SEOM-GECP-GETTHI Clinical Guidelines for the treatment of patients with thymic epithelial tumours (2021)

Chemotherapy; Lenvatinib; Thymic epithelial tumoursQuimioterapia; lenvatinib; Tumores epiteliales tímicosQuimioteràpia; Lenvatinib; Tumors epitelials tímicsThymic epithelial tumours (TET) represent a heterogeneous group of rare malignancies that include thymomas and thymic carcinoma. Treatment of TET is based on the resectability of the tumour. If this is considered achievable upfront, surgical resection is the cornerstone of treatment. Platinum-based chemotherapy is the standard regimen for advanced TET. Due to the rarity of this disease, treatment decisions should be discussed in specific multidisciplinary tumour boards, and there are few prospective clinical studies with new strategies. However, several pathways involved in TET have been explored as potential targets for new therapies in previously treated patients, such as multi-tyrosine kinase inhibitors with antiangiogenic properties and immune checkpoint inhibitors (ICI). One third of patient with thymoma present an autoimmune disorders, increasing the risk of immune-related adverse events and autoimmune flares under ICIs. In these guidelines, we summarize the current evidence for the therapeutic approach in patients with TET and define levels of evidence for these decisions

Enterprise Ionic Liquids Database (ILUAM) for Use in Aspen ONE Programs Suite with COSMO-Based Property Methods

“This document is the Accepted Manuscript version of a Published Work that appeared in final form in Industrial & Engineering Chemistry Research copyright © American Chemical Society after peer review and technical editing by the publisher . To access the final and published work see Enterprise Ionic Liquids Database (ILUAM) for Use in Aspen ONE Programs Suite with COSMO-Based Property Methods V. R. Ferro, C. Moya, D. Moreno, R. Santiago, J. de Riva, G. Pedrosa, M. Larriba, I. Diaz, and J. Palomar Industrial & Engineering Chemistry Research 2018 57 (3), 980-989 DOI: 10.1021/acs.iecr.7b04031An enterprise database of pure ionic liquids (ILs) for its use in the Aspen ONE programs is presented. The database is identified as ILUAM, and the first version (ILUAM01) contains 100 ILs composed of 30 cations and 23 anions. The IL components were introduced in Aspen Properties as pseudocomponents using information from the computational COSMO-RS method and from experimental viscosity data. ILUAM database was created to be used along with the COSMOSAC property model implemented in Aspen Plus, allowing evaluating IL process performance without needing further experimental data. Some validation tests were carried out to demonstrate the successful incorporation of ILs in the Aspen Plus property system. Then, the performance of ILUAM01 database in thermodynamic property predictions of mixtures involving ILs and conventional chemical compounds was revised in terms of activity coefficients at infinite dilution and phase equilibrium data. The property description of pure ILs and IL mixtures with conventional chemical compounds using COSMO-based/Aspen Plus approach was found with the accuracy level required in the conceptual design of new processes. ILUAM database offers the opportunity of performing systematic evaluation of potential industrial applications of ILs and their competitiveness as alternative to conventional solvents.The authors are grateful to the Comunidad de Madrid (project S2013- MAE-2800) and to the Ministerio de Economía y Competitividad of Spain (Project CTQ2014-52288-R) for financial support. M. Larriba also thanks Ministerio de Economía y Competitividad of Spain for awarding him a Juan de la Cierva-Formación Contract (Reference FJCI-2015-25343

Cypher: An Evolving Query Language for Property Graphs

International audienceThe Cypher property graph query language is an evolving language, originally designed and implemented as part of the Neo4j graph database, and it is currently used by several commercial database products and researchers. We describe Cypher 9, which is the first version of the language governed by the openCypher Implementers Group. We first introduce the language by example, and describe its uses in industry. We then provide a formal semantic definition of the core read-query features of Cypher, including its variant of the property graph data model, and its " ASCII Art " graph pattern matching mechanism for expressing subgraphs of interest to an application. We compare the features of Cypher to other property graph query languages, and describe extensions, at an advanced stage of development, which will form part of Cypher 10, turning the language into a compositional language which supports graph projections and multiple named graphs

Protumorigenic effects of Snail-expression fibroblasts on colon cancer cells

et al.Snail1 is a transcriptional factor that plays an important role in epithelial–mesenchymal transition and in the acquisition of invasive properties by epithelial cells. In colon tumors, Snail1 expression in the stroma correlates with lower specific survival of cancer patients. However, the role(s) of Snail1 expression in stroma and its association with patients' survival have not been determined. We used human primary carcinoma-associated fibroblasts (CAFs) or normal fibroblasts (NFs) and fibroblast cell lines to analyze the effects of Snail1 expression on the protumorigenic capabilities in colon cancer cells. Snail1 expression was higher in CAFs than in NFs and, as well as α-SMA, a classic marker of activated CAFs. Moreover, in tumor samples from 50 colon cancer patients, SNAI1 expression was associated with expression of other CAF markers, such as α-SMA and fibroblast activation protein. Interestingly, coculture of CAFs with colon cells induced a significant increase in epithelial cell migration and proliferation, which was associated with endogenous SNAI1 expression levels. Ectopic manipulation of Snail1 in fibroblasts demonstrated that Snail1 expression controlled migration as well as proliferation of cocultured colon cancer cells in a paracrine manner. Furthermore, expression of Snail1 in fibroblasts was required for the coadjuvant effect of these cells on colon cancer cell growth and invasion when coxenografted in nude mice. Finally, cytokine profile changes, particularly MCP-3 expression, in fibroblasts are put forward as mediators of Snail1-derived effects on colon tumor cell migration. In summary, these studies demonstrate that Snail1 is necessary for the protumorigenic effects of fibroblasts on colon cancer cells.This research was supported by the PI12/02037, Fundación Científica AECC, SAF2010-20750, S2010/BMD-2344, RTICC-RD12/0036/0041 and by the Fundación Banco Santander. Antonio García de Herreros’ laboratory was supported by RTICC-RD12/0036/0005 and SAF 2010-16089. Ma Jesús Larriba’s laboratory was supported by RD12/0036/0021. Cristina Peña and José Miguel García are recipients of Miguel Servet Contracts from the Instituto de Salud Carlos III.Peer reviewe

1386pdimpower150 clinical safety tolerability and immune related adverse events in a phase iii study of atezolizumab atezo chemotherapy chemo bevacizumab bev vs chemo bev in 1l nonsquamous nsclc

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Assessment of the psychosocial and economic impact according to sex in non-small cell lung cancer patients: an exploratory longitudinal study

Background: Little is known about the impact of sex on lung cancer patients from the psychological, economic and social perspectives. This study was designed to explore the psychosocial and economic impact according to sex of metastatic non-small cell lung cancer (mNSCLC) in patients and caregivers. Methods: Exploratory study of two cohorts of patients starting first-line treatment for mNSCLC. The following questionnaires were administered at baseline, 4 months later and following the first and second disease progression: APGAR, relationship impact scale, DUKE-UNC scale, economic impact in patients and caregiver, and Zarit scale. It was planned to include 1250 patients to get an 80% possibility of detecting as significant (p < 0.05) effect sizes less than 0.19 between men and women. Univariate comparisons were made between the tests applied to men and women. Overall survival was estimated with Kaplan–Meier method. Cox analyses were done to estimate hazard ratios (HRs) with 95% CI. Results: 333 patients were included. Most families reported to continue being functional despite the lung cancer diagnosis. Regardless of sex, they did not perceive changes in their partner relationship. Most patients felt their social support was normal. Roughly 25% of people reported a worsening in their economic situation, without remarkable differences by sex. Statistically significant differences were found between both groups regarding the caregiver’s relationship to the patient (more parents were the caregiver in females than in males, p < 0.0001) and the caregiver’s employment situation (more employed caregivers in females) (p < 0.0001). Most caregivers of both sexes considered that taking care of their relative did not pose a significant burden. Conclusions: This study provides a preliminary insight into sex-related characteristics in the management of advanced NSCLC and its impact on the emotional, social and economic burden of patients and their caregivers, and recall the high priority of researching in cancer from a sex perspective. Nevertheless, due to the low recruitment rate and the relevant loss of patients during the follow-up, it was difficult to find differences by sex. Trial registration: ClinicalTrials.gov identifier: NCT02336061. Ethics committee: Comité Ético de Investigación Clínica del Hospital Clínic de Barcelona, Spain. Reference number: HCB/2014/0705

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

Prospective Exploratory Analysis of Angiogenic Biomarkers in Peripheral Blood in Advanced NSCLC Patients Treated With Bevacizumab Plus Chemotherapy: The ANGIOMET Study

Finding angiogenic prognostic markers in advanced non-small-cell lung cancer is still an unmet medical need. We explored a set of genetic variants in the VEGF-pathway as potential biomarkers to predict clinical outcomes of patients with non-small-cell lung cancer treated with chemotherapy plus bevacizumab. We prospectively analyzed the relationship between VEGF-pathway components with both pathological and prognostic variables in response to chemotherapy plus bevacizumab in 168 patients with non-squamous non-small-cell lung cancer. Circulating levels of VEGF and VEGFR2 and expression of specific endothelial surface markers and single-nucleotide polymorphisms in VEGF-pathway genes were analyzed. The primary clinical endpoint was progression-free survival. Secondary endpoints included overall survival and objective tumor response. VEGFR-1 rs9582036 variants AA/AC were associated with increased progression-free survival (p = 0.012 and p = 0.035, respectively), and with improved overall survival (p = 0.019) with respect to CC allele. Patients with VEGF-A rs3025039 harboring allele TT had also reduced mortality risk (p = 0.049) compared with the CC allele. The VEGF-A rs833061 variant was found to be related with response to treatment, with 61.1% of patients harboring the CC allele achieving partial treatment response. High pre-treatment circulating levels of VEGF-A were associated with shorter progression-free survival (p = 0.036). In conclusion, in this prospective study, genetic variants in VEGFR-1 and VEGF-A and plasma levels of VEGF-A were associated with clinical benefit, progression-free survival, or overall survival in a cohort of advanced non-squamous non-small-cell lung cancer patients receiving chemotherapy plus antiangiogenic therapy. © Copyright © 2021 Jantus-Lewintre, Massutí Sureda, González Larriba, Rodríguez-Abreu, Juan, Blasco, Dómine, Provencio Pulla, Garde, Álvarez, Maestu, Pérez de Carrión, Artal, Rolfo, de Castro, Guillot, Oramas, de las Peñas, Ferrera, Martínez, Serra, Rosell and Camps

Weekly administration of docetaxel in combination with estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer: final results from a phase II study

The objective of this study was to evaluate the efficacy and safety profile of weekly docetaxel, estramustine and celecoxib in patients with advanced hormone-refractory prostate cancer. Forty-eight patients received 35 mg m−2 of weekly docetaxel for 3 out of every 4 weeks, 280 mg of estramustine twice daily on days 1–3, 8–10, 15–17 and 400 mg of celecoxib twice daily until progression or toxicity. Cycles were repeated every 28 days for at least six cycles. Patients were evaluated for response and toxicity. Patients received a median of four cycles (range: 1–9). On an intention-to-treat analysis, prostate-specific antigen (PSA) was decreased greater than 50% in 28 out of 48 patients (overall response rate: 58%, 95% confidence interval (CI): 44–72) and median duration of PSA response was 8.0 months (95% CI: 6.9–9.0). After a median follow-up of 11.3 months, the median time to progression was 7.1 months and the median overall survival was 19.2 months. The most frequent severe toxicity was asthenia (15% of patients), diarrhoea and stomatitis (8% of patients, each). Grade 3/4 neutropenia was reported in two patients. There was a toxic death during the study due to a gastric perforation. Celecoxib with weekly docetaxel and estramustine is an effective and safe treatment for patients with hormone-refractory prostate cancer, but it does not seem to add any benefit to docetaxel