Development of an innovative validation strategy of gas–surface interaction modelling for re‑entry applications

Abstract This paper summarises the final synthesis of an ESA technology research programme entitled “Development of an Innovative Validation Strategy of Gas Surface Interaction Modelling for Re-entry Applications”. The focus of the project was to demonstrate the correct pressure dependency of catalytic surface recombination, with an emphasis on Low Earth Orbit (LEO) re-entry conditions and thermal protection system materials. A physics-based model describing the prevalent recombination mechanisms was proposed for implementation into two CFD codes, TINA and TAU. A dedicated experimental campaign was performed to calibrate and validate the CFD model on TPS materials pertinent to the EXPERT space vehicle at a wide range of temperatures and pressures relevant to LEO. A new set of catalytic recombination data was produced that was able to improve the chosen model calibration for CVD-SiC and provide the first model calibration for the Nickel–Chromium super-alloy PM1000. The experimentally observed pressure dependency of catalytic recombination can only be reproduced by the Langmuir–Hinshelwood recombination mechanism. Due to decreasing degrees of (enthalpy and hence) dissociation with facility stagnation pressure, it was not possible to obtain catalytic recombination coefficients from the measurements at high experimental stagnation pressures. Therefore, the CFD model calibration has been improved by this activity based on the low pressure results. The results of the model calibration were applied to the existing EXPERT mission profile to examine the impact of the experimentally calibrated model at flight relevant conditions. The heat flux overshoot at the CVDSiC/PM1000 junction on EXPERT is confirmed to produce radiative equilibrium temperatures in close proximity to the PM1000 melt temperature.This was anticipated within the margins of the vehicle design; however, due to the measurements made here for the first time at relevant temperatures for the junction, an increased confidence in this finding is placed on the computations

Cost analysis of the management of brain metastases in patients with advanced ALK+ NSCLC: alectinib versus crizotinib

Aim: To estimate management cost of NSCLC ALK+ patients with and without brain metastasis (BM), and to compare annual costs in patients treated with alectinib or crizotinib. Methods: Management cost/year (euro 2018) in patients with and without BM was estimated with disaggregated resource consumption provided by local oncologists, including medical visits, hospitalizations, diagnostic/laboratory tests, imaging techniques and surgical procedures. The comparison of costs/year with alectinib and crizotinib, considered the cumulative 12-month incidence of BM in ALEX trial (9.4 and 41.4%, respectively). Results: Management cost was euro6173.42/patient-year without BM and euro21,637.50/patient-year with BM. With alectinib, average cost/patient was lower than crizotinib (euro4948.51/patient-year). Conclusion: Prevention of BM with alectinib may result in reductions of cost/year in the management of advanced ALK+ NSCLC

HYDRA: Macroscopic modeling of hybrid ablative thermal protection system

In the framework of HYDRA, an European funded program, technological solutions of hybrid Thermal Protection System (TPS) are developed. This advanced shielding relies on the hybridization of upper lightweight porous ablative material and inner Ceramic Matrix Composite (CMC) bonded together with a novel high temperature adhesive. The aerial mass optimization of the full TPS requires a controlled reduction in the ablative material thickness to reach high operating temperature configuration of the CMC. Therefore, radiative heat transfer takes place in a thin layer of ablator and becomes a major contributor to the elevation of the interface temperature. In this paper we develop an high fidelity radiative transfer in porous carbon fibers charring and ablative material. Specific elementary characterization, plasma test campaign and numerical simulation are scheduled to feed this radiative heat transfer model

First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

BackgroundTreatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC.MethodsFrail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. Main objective: to assess progression-free survival (PFS) rate at 6months. Treatment consisted of 28-daycycles of orally administered regorafenib 160mg/day (3 weeks followed by 1 week rest).ResultsForty-seven patients were included in the study. Median age was 81years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6months (95%CI 2.7-8.4). Median overall survival (OS) was 16months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%).ConclusionsThe study did not meet the pre-specified boundary of 55% PFS rate at 6months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach.Trial registrationThis trial was prospectively registered at EudraCT (2013-000236-94). Date of trial registration: April 9th, 2013

LungBEAM: A prospective multicenter study to monitor stage IV NSCLC patients with EGFR mutations using BEAMing technology

Objectives: The aim of LungBEAM was to determine the value of a novel epidermal growth factor receptor (EGFR) mutation test in blood based on BEAMing technology to predict disease progression in advanced non-small cell lung cancer (NSCLC) patients treated with first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Another goal was to monitor the dynamics of EGFR mutations, as well as to track EGFR exon 20 p.T790M (p.T790M) resistance during treatment, as critical indicators of therapeutic efficacy and patient survival. Methods: Stage IV NSCLC patients with locally confirmed EGFR-TKI sensitizing mutations (ex19del and/or L858R) in biopsy tissue who were candidates to receive first- or second-generation EGFR-TKI as first-line therapy were included. Plasma samples were obtained at baseline and every 4 weeks during treatment until a progression-free survival (PFS) event or until study completion (72-week follow-up). The mutant allele fraction (MAF) was determined for each identified mutation using BEAMing. Results: A total of 68 of the 110 (61.8%) patients experienced a PFS event. Twenty-six patients (23.6%) presented with an emergent p.T790M mutation in plasma at some point during follow-up, preceding radiologic progression with a median of 76 (interquartile ratio: 54–111) days. Disease progression correlated with the appearance of p.T790M in plasma with a hazard ratio (HR) of 1.94 (95% confidence interval [CI], 1.48–2.54; p < 0.001). The HR for progression in patients showing increasing plasma sensitizing mutation levels (positive MAF slope) versus patients showing either decreasing or unchanged plasma mutation levels (negative or null MAF slopes) was 3.85 (95% CI, 2.01–7.36; p < 0.001). Conclusion: Detection and quantification of EGFR mutations in circulating tumor DNA using the highly sensitive BEAMing method should greatly assist in optimizing treatment decisions for advanced NSCLC patients. © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

Reflections on the IASLC 12th World Conference on Lung Cancer

Editorial.--El pdf es la versión post-print.Peer Reviewe

Cursillo de Introducción a las Investigaciones Pesqueras : Programa

Programa del Cursillo de Introducción a las Investigaciones Pesqueras organizado por la Sección de Biología Marina del Instituto de Biología Aplicada de Barcelona (IBA-CSIC) y celebrado del 15 de marzo al 15 de julio de 1949 en el laboratorio de Zoología de la Universitat de Barcelona (UB) y en las instalaciones del Jardín Botánico «Mar i Murtra» de Blanes.-- 1 pagePeer reviewe