Publications by authors named "Steve Olsen"

Introduction: The presence of minimal residual disease (MRD) after curative-intent surgery for early-stage cancers is associated with disease recurrence. Circulating tumour deoxyribonucleic acid (ctDNA) has emerged as a promising biomarker for MRD assessment in patients with colorectal cancer (CRC) who have undergone surgery or completed adjuvant therapy. MRD tests are already available for use in clinics; however, treatment decisions following MRD results obtained in routine practice are infrequently described.

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Introduction: Next-generation sequencing (NGS) of tumor DNA can detect actionable drivers and help guide therapy for patients with advanced-stage cancers. While tissue-based genotyping is considered a standard of care, blood-based genotyping is emerging as a valid alternative. Tumor genomic profiles may vary by region, and data from the Middle East and North Africa (MENA) are not widely available.

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Article Synopsis
  • Next-generation sequencing (NGS) of plasma cell-free DNA can detect driver mutations in advanced non-small cell lung cancer (NSCLC) and might enhance standard molecular evaluations, though its initial utility remains unclear.
  • A randomised study on 180 patients with suspected advanced NSCLC compared two groups: one receiving NGS results after tissue genotyping and the other receiving them sooner; results showed earlier NGS led to a shorter wait for treatment (20 days vs. 28 days).
  • The study found high agreement between liquid NGS and tissue testing, identifying mutations in nearly 43% of cases where tissue tests were negative.
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Objectives: Plasma-based comprehensive circulating cell-free DNA (cfDNA) next generation sequencing (NGS) has shown utility in advanced non-small cell lung cancer (aNSCLC). The aim of this study was to determine the feasibility of cfDNA-based NGS to identify actionable gene alterations in patients with aNSCLC.

Patients And Methods: This single-center non-interventional retrospective study evaluated Korean patients with biopsy-confirmed stage III/IV non-squamous aNSCLC.

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Background: fusions have been reported infrequently in aNSCLC, including as a rare, acquired resistance mechanism following treatment with EGFR TKIs. Data regarding their prevalence and therapeutic implications are limited.

Methods: The Guardant Health (GH) electronic database (ED) was evaluated for cases of aNSCLC and fusions; fusion prevalence with and without a co-existing mutation was assessed.

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Background: Patients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) inevitably acquire resistance to ALK inhibitors. Longitudinal monitoring of cell-free plasma DNA (cfDNA) next-generation sequencing (NGS) could predict the response and resistance to tyrosine kinase inhibitor (TKI) therapy in ALK+ NSCLC.

Methods: Patients with ALK+ NSCLC determined by standard tissue testing and planned to undergo TKI therapy were prospectively recruited.

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Plasma-based next-generation sequencing (NGS) has demonstrated the potential to guide the personalized treatment of non-small cell lung cancer (NSCLC). Inherent differences in mutational genomic profiles of NSCLC exist between Asian and Western populations. However, the published mutational genomic data of NSCLC has largely focused on Western populations.

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The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis ( UMIN000027887 ). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC.

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Article Synopsis
  • The study investigates how to differentiate between focal gene amplification (amp) and aneuploidy in advanced solid tumors using next-generation sequencing of circulating free DNA (cfDNA).
  • A total of 1,025 patients were analyzed, with the researchers employing a specific algorithm to identify focal amps before and after a system upgrade of the sequencing panel.
  • The findings revealed that focal amp was present in 3.7% of patients, primarily in lung and gastroesophageal cancers, suggesting a relevant approach for targeted therapy in oncogenic cases.
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Background: Because of the growing number of actionable biomarkers in non-small cell lung cancer (NSCLC), sufficient tissue availability for testing is becoming a greater challenge. Liquid biopsy offers a potential solution by complementing standard tissue-based methods. In this study, the authors analyzed the concordance of actionable genomic alterations sequenced from circulating tumor DNA (ctDNA; Guardant360) and tissue (Oncomine Focus Assay).

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Shared decision-making (SDM) is a collaborative approach to making decisions in health care, and is a cornerstone of person-centered care. While providers are increasingly expected to utilize SDM in routine practice, widespread and sustainable implementation has proven difficult, especially in the care of individuals diagnosed with serious mental illnesses, and physicians and patients continue to identify barriers to effective collaboration. To date, SDM research has largely focused on the provision of high-quality clinical information from doctors to patients to the neglect of what may be the most important, and transformative, aspect of SDM-the relationship itself.

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Purpose: HER2-positive breast cancer is heterogeneous. Some tumors express mutations, like activating PIK3CA mutations or reduced PTEN expression, that negatively correlate with response to HER2-targeted therapies. In this exploratory analysis, we investigated whether the efficacy of trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprised of the cytotoxic agent DM1 linked to the HER2-targeted antibody trastuzumab, was correlated with the expression of specific biomarkers in the phase III EMILIA study.

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Purpose: Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC) comprising the cytotoxic agent DM1 conjugated to trastuzumab with a stable linker. Thrombocytopenia was the dose-limiting toxicity in the phase I study, and grade ≥3 thrombocytopenia occurred in up to 13% of patients receiving T-DM1 in phase III studies. We investigated the mechanism of T-DM1-induced thrombocytopenia.

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Background And Objective: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer previously treated with trastuzumab and taxane chemotherapy. It comprises the microtubule inhibitory cytotoxic agent DM1 conjugated to the HER2-targeted humanized monoclonal antibody trastuzumab via a stable linker. To characterize the pharmacokinetics of T-DM1 in patients with metastatic breast cancer, concentrations of multiple analytes were quantified, including serum concentrations of T-DM1 conjugate and total trastuzumab (the sum of conjugated and unconjugated trastuzumab), as well as plasma concentrations of DM1.

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Our objective in this prospective study was to determine the natural course of Brucella abortus infection in cohorts of seropositive and seronegative, female bison (Bison bison) and their offspring in Yellowstone National Park (YNP) for 5 yr. We collected specimens from 53 adult females and 25 calves at least once and from 45 adults and 22 calves more than once. Annual seroconversion rates (negative to positive) were relatively high (23% for calves and juvenile bison, 6% in the total sample of adult female bison in our study, and 11% in the adult females that began the study as seronegatives).

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Whereas the genesis of an arterial lesion is thought to be the result of migration and proliferation of vascular cells, recent insights into the biology of progenitor cells now question this concept. Specifically, endothelial and smooth muscle cells appear to be derived from multiple sources such as circulating stem and progenitor cells, as well as tissue-resident progenitor cell populations. These cells may engraft at sites of vascular injury and play an integral role in vascular repair.

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Hepatic lipidosis, a hallmark lesion of lipid mobilization disorders in ruminants, was noted in four 3-year-old, pregnant bison (Bison bison) after periods of anorexia that progressed to recumbency and death. The affected bison were part of a herd at the National Animal Disease Center (NADC) that was used for brucellosis vaccine research. Microscopically, the liver contained swollen hepatocytes with numerous, variably sized, round, smoothly contoured vacuoles that displaced cytoplasmic structures.

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