Background: Adjuvant therapy with durvalumab, with or without tremelimumab, may have efficacy in patients with limited-stage small-cell lung cancer who do not have disease progression after standard concurrent platinum-based chemoradiotherapy.
Methods: In a phase 3, double-blind, randomized, placebo-controlled trial, we assigned patients to receive durvalumab at a dose of 1500 mg, durvalumab (1500 mg) plus tremelimumab at a dose of 75 mg (four doses only), or placebo every 4 weeks for up to 24 months. Randomization was stratified according to disease stage (I or II vs.
Introduction: Body contouring procedures are commonly performed in the United States for patients seeking to sculpt specific areas of their bodies. The aim of this study was to provide an updated analysis of the factors that influence medical malpractice litigation surrounding body contouring surgery.
Methods: The following terms were used to search the Westlaw Campus Legal research Database for cases with earliest documentation after January 2013: ("contouring" OR "abdominoplasty" OR "liposuction" OR "tummy tuck" OR "body lift" OR "thigh lift" OR "arm lift" OR "brachioplasty" OR "thighplasty" OR "lipectomy" OR "panniculectomy") AND "surgery" AND "medical malpractice.
Objectives: This report focuses on lurbinectedin activity and safety in a subgroup of small cell lung cancer (SCLC) patients from a Basket phase 2 study (Trigo et al. Lancet Oncology 2020;21:645-654) with chemotherapy-free interval (CTFI) ≥ 30 days. This pre-planned analysis was requested for obtaining regulatory approval of lurbinectedin in Switzerland.
View Article and Find Full Text PDFMalignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4-8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.
View Article and Find Full Text PDFPurpose: The phase III SKYSCRAPER-02 study determined whether the benefits of atezolizumab plus carboplatin and etoposide (CE) could be enhanced by the addition of tiragolumab in untreated extensive-stage small-cell lung cancer (ES-SCLC). We report final progression-free survival (PFS) and overall survival (OS) analyses.
Methods: Patients received tiragolumab 600 mg/placebo, plus atezolizumab 1,200 mg and CE (four cycles), then maintenance tiragolumab/placebo plus atezolizumab.
Introduction: In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly ( = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of life (HRQoL) results from KEYNOTE-604.
View Article and Find Full Text PDFBackground: ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes.
Methods: In this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×10 virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone.
MPM is an aggressive disease with an immunosuppressive tumor microenvironment, and interest in exploring immunotherapy in this disease has been increasing. In the first line of treatment, the combination of nivolumab and ipilimumab demonstrated an improvement in survival over chemotherapy. The presence of TILs has been recognized as a marker of antitumor immune response to chemotherapy in solid tumors.
View Article and Find Full Text PDFImmune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis are the main therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) without a druggable oncogenic alteration. Nevertheless, only a portion of patients benefit from this type of treatment. Here, we assessed the value of shallow whole-genome sequencing (sWGS) on plasma samples to monitor ICI benefit.
View Article and Find Full Text PDFClimate-driven biodiversity erosion is escalating at an alarming rate. The pressure imposed by climate change is exceptionally high in tropical ecosystems, where species adapted to narrow environmental ranges exhibit strong physiological constraints. Despite the observed detrimental effect of climate change on ecosystems at a global scale, our understanding of the extent to which multiple climatic drivers affect population dynamics is limited.
View Article and Find Full Text PDFBackground: Lurbinectedin is a synthetic marine-derived anticancer agent that acts as a selective inhibitor of oncogenic transcription. Lurbinectedin monotherapy (3·2 mg/m every 3 weeks) received accelerated approval from the US Food and Drug Administration on the basis of efficacy in patients with small-cell lung cancer (SCLC) who relapsed after first-line platinum-based chemotherapy. The ATLANTIS trial assessed the efficacy and safety of combination lurbinectedin and the anthracycline doxorubicin as second-line treatment for SCLC.
View Article and Find Full Text PDFPorcine brucellosis, caused by (), is a notifiable disease causing significant economic losses in production systems. Most infected pigs may act as carriers and shed even if asymptomatic. This can contribute to environmental persistence, thus hindering control efforts.
View Article and Find Full Text PDFIn recent years, immunotherapy-based regimens have been included into the treatment's algorithm of several cancer types. Programmed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) interact with their ligands found on the surface of antigen presenting cells (APC) or tumor cells (PD-L1/2 and CD80/86). Through these interactions, stimulatory or inhibitory signals are established.
View Article and Find Full Text PDFBackground: Immune checkpoint inhibitors (ICIs) targeting the programmed cell death 1/programmed death-ligand 1 axis have transformed the management of advanced non-small cell lung cancer (NSCLC). However, many patients do not benefit from this type of treatment, and thus several molecular biomarkers of benefit have been explored. The value of somatic copy number alterations (SCNAs) burden remains elusive.
View Article and Find Full Text PDFBackground: Preclinical data show that the combination of an ALK inhibitor (ALKi) with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) may act synergistically to overcome drug resistance mechanisms. Here, we assessed the safety, tolerability, and preliminary clinical activity of ceritinib, an ALKi in combination with ribociclib, a CDK4/6i, in patients with ALK-rearranged non-small cell lung cancer (NSCLC).
Methods: This was a multicenter, open-label, phase Ib/II dose-escalation study to determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) for ceritinib plus ribociclib therapy.
Introduction: Topotecan is approved as second-line treatment for small cell lung cancer (SCLC). Irinotecan is also frequently used given its more convenient schedule and superior tolerability. Preclinical studies support disialoganglioside (GD2) as an SCLC target and the combination of dinutuximab, an anti-GD2 antibody, plus irinotecan in this setting.
View Article and Find Full Text PDFBackground: RESILIENT (NCT03088813) is a phase 2/3 study assessing the safety, tolerability, and efficacy of liposomal irinotecan monotherapy in patients with small cell lung cancer and disease progression on/after first-line platinum-based therapy. Here, we present results from RESILIENT part 1.
Methods: This open-label, single-arm, safety run-in evaluation with dose-exploration and dose-expansion phases included patients ≥18 years old with Eastern Cooperative Oncology Group performance status of 0/1; those with asymptomatic central nervous system metastases were eligible.
Introduction: The addition of immune checkpoint inhibitors (ICIs) to conventional chemotherapy (CT) as first-line treatment improves survival in extensive-stage small-cell lung cancer (ES-SCLC). The aim of this meta-analysis was to determine the relative efficacy of first-line ICIs compared with CT in patients with ES-SCLC.
Methods: Two independent reviewers extracted relevant data according to PRISMA guidelines and assessed the risk of bias using the Cochrane Collaboration's risk-of-bias tool.
Introduction: SCLC is one of the most lethal malignancies. Classically, staging has been performed using a dual classification distinguishing limited from the extensive stage. This study aimed to evaluate the prognostic value of TNM staging in a real-world population of patients with SCLC.
View Article and Find Full Text PDFA frequently encountered problem with imaging budding yeast specimens by light microscopy is that the cells do not adhere well to glass microscope slides. Frustratingly, cells that initially appear stationary in the visual field often become displaced and float away. The development of immunofluorescence microscopy methods for yeast led to the widespread use of poly-l-lysine as an adhesive for cell immobilization.
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