Why History Education?

Diese englischsprachige Publikation präsentiert eine ganze Reihe von Gründen, warum Geschichte heute unbedingt unterrichtet werden muss. Sie liest sich als Plädoyer für einen kompetenten Umgang mit Geschichte in heutigen Gesellschaften.+ ID der Publikation: phlu_17599 + Art des Beitrages: Sammelband + Sprache: Englisch + Letzte Aktualisierung: 2023-11-14 09:26:0

Real-World Treatment Patterns and Survival Outcome in Advanced Anaplastic Lymphoma Kinase (ALK) Rearranged Non-Small-Cell Lung Cancer Patients

Introduction: Survival of ALK-rearranged NSCLC patients has dramatically improved by the use of multiple ALK-tyrosine kinase inhibitors (ALK-TKI). However, still little is known about the impact of drug sequencing and clinical features on survival in a real-world setting. Methods: Patients with stage IV ALK-rearranged NSCLC treated at six centers in Switzerland and Italy were identified and standard clinical variables collected. OS curves were constructed using the Kaplan-Meier method and compared with the log-rank test. Multivariate Cox proportional hazard analysis was applied to determine the correlations between clinical features and OS. In four patients, biopsies were subjected to NGS. Results: One-hundred and twenty-one patients with stage IV ALK-rearranged NSCLC diagnosed between 2011 and 2016 were included. With a median follow-up time of 39.5 months, the median OS from diagnosis of stage IV disease was 48.0 months. First-line treatment consisted of an ALK-TKI in 24% of patients, with crizotinib in 83% of them. Chemotherapy as first-line treatment did not influence OS (p = 0.955). The use of more than one ALK-TKI line positively correlated with OS (p = 0.016), as well as the use of alectinib or lorlatinib in any treatment line, as compared to the use of crizotinib ± ceritinib (p = 0.022). A never smoking history was an independent prognostic factor for OS (p = 0.032). Moreover, treatment with alectinib significantly improved OS. Conclusions: Targeted treatment for ALK-positive NSCLC patients lead to prolonged OS. Smoking status was a negative independent prognostic factor in a multi-variate analysis. The use of alectinib or lorlatinib in any treatment line improved overall outcome

Phase 2 trial of single-agent everolimus in chemotherapy-naive patients with castration-resistant prostate cancer (SAKK 08/08)

BACKGROUND: The phosphatase and tensin homolog (PTEN) tumor suppressor gene is deregulated in many advanced prostate cancers, leading to activation of the phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway and thus increased cell survival. OBJECTIVE: To evaluate everolimus, an inhibitor of mTOR, in patients with metastatic castration-resistant prostate cancer (mCRPC), and to explore potentially predictive serum biomarkers by proteomics, the significance of PTEN status in tumor tissue, and the impact of everolimus on immune cell subpopulations and function. DESIGN, SETTING, AND PARTICIPANTS: A total of 37 chemotherapy-naive patients with mCRPC and progressive disease were recruited to this single-arm phase 2 trial (ClinicalTrials.gov identifier NCT00976755). INTERVENTION: Everolimus was administered continuously at a dose of 10mg daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was progression-free survival (PFS) at 12 wk defined as the absence of prostate-specific antigen (PSA), radiographic progression, or clinical progression. Groups were compared using Wilcoxon rank-sum tests or Fisher exact tests for continuous and discrete variables, respectively. Time-to-event end points were analyzed using the Kaplan-Meier method and univariate Cox regression. RESULTS AND LIMITATIONS: A total of 13 patients (35%; 95% confidence interval, 20-53) met the primary end point. Confirmed PSA response ≥50% was seen in two (5%), and four further patients (11%) had a PSA decline ≥30%. Higher serum levels of carboxypeptidase M and apolipoprotein B were predictive for reaching the primary end point. Deletion of PTEN was associated with longer PFS and response. Treatment was associated with a dose-dependent decrease of CD3, CD4, and CD8 T lymphocytes and CD8 proliferation and an increase in regulatory T cells. Small sample size was the major limitation of the study. CONCLUSIONS: Everolimus activity in unselected patients with mCRPC is moderate, but PTEN deletion could be predictive for response. Several serum glycoproteins were able to predict PFS at 12 wk. Prospective validation of these potential biomarkers is warranted. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov with the identifier NCT00976755. Results of this study were presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology (June 3-7, 2011; Chicago, IL, USA) and the annual meeting of the German, Austrian, and Swiss Societies for Oncology and Hematology (September 30-October 4, 2011; Basel, Switzerland)