Medication Prescribing Errors on a Surgery Service - Addressing the Gap with a Curriculum for Surgery Residents: A Prospective Observational Study.

Objectives: Educational interventions with proven effectiveness to reduce medication prescribing errors are currently lacking. Our objective was to implement and assess the effectiveness of a curriculum to reduce medication prescribing errors on a surgery service.

Methods: This was a prospective observational cohort study at a Canadian academic hospital without an electronic order entry system.

Pan-tumor survey of ROS1 fusions detected by next-generation RNA and whole transcriptome sequencing.

Background: Two ROS1 tyrosine kinase inhibitors have been approved for ROS1 fusion positive (ROS1+) non-small cell lung cancer (NSCLC) tumors. We performed a pan-tumor analysis of the incidence of ROS1 fusions to assess if more ROS1+ patients who could benefit from ROS1 TKIs could be identified.

Methods: A retrospective analysis of ROS1 positive solid malignancies identified by targeted RNA sequencing and whole transcriptome sequencing of clinical tumor samples performed at Caris Life Science (Phoenix, AZ).

Lorlatinib Tolerability and Association With Clinical Outcomes in Patients With Advanced - or -Rearranged NSCLC: A Brief Report.

Introduction: Treatment with lorlatinib for patients with advanced - and -rearranged NSCLC (+ and + NSCLC) is associated with a unique set of adverse events (AEs) often requiring dose reduction. However, the impact of dose reductions on outcomes remains unclear and is mainly limited to analyses from prospective studies of lorlatinib in the first-line setting.

Methods: We reviewed the course of 144 patients with advanced or -rearranged NSCLC treated with lorlatinib in the second-line or later setting to assess the frequency of dose reductions resulting from treatment-related AEs (TRAEs) and the association between dose reductions and progression-free survival (PFS) and overall survival (OS).

CodeBreak 200: Sotorasib Has Not Broken the KRAS Enigma Code.

Thirteen percent of non-small cell lung cancer (NSCLC) patients are estimated to have the KRAS G12C mutation. Sotorasib is a novel KRAS G12C inhibitor that has shown promising results in preclinical and clinical studies, granting its conditional approval by the FDA in May 2021. The phase I clinical trial resulted in a confirmed response of 32% and progression free survival (PFS) of 6.

Low-Dose Computed Tomography (LDCT) Lung Cancer Screening in Asian Female Never-Smokers Is as Efficacious in Detecting Lung Cancer as in Asian Male Ever-Smokers: A Systematic Review and Meta-Analysis.

Introduction: Lung cancer in never-smokers is the major cancer cause of death globally. We compared the efficacy of low-dose computed tomography (LDCT) lung cancer screening among never-smokers versus ever-smokers using systematic review and meta-analysis.

Methods: LDCT lung cancer screening studies that simultaneously included both ever-smoker and never-smoker participants published by April 30, 2021, were searched through PubMed and Scopus.

Spotlight on Furmonertinib (Alflutinib, AST2818). The Swiss Army Knife (del19, L858R, T790M, Exon 20 Insertions, "uncommon-G719X, S768I, L861Q") Among the Third-Generation EGFR TKIs?

Osimertinib, a third-generation (3G) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is now considered the standard of care for the first-line (1L) treatment of advanced + NSCLC due to statistically significant improved progression-free survival (PFS) and overall survival (OS) compared with first-generation (1G) treatment from the FLAURA trial. Recently two other 3G EGFR TKIs (aumolertinib and furmonertinib) have been approved in China for treatment of T790M+ NSCLC. Randomized Phase 3 trials of these two 3G EGFR TKIs have also demonstrated PFS over gefitinib respectively.

A High Percentage of NSCLC With Germline Mutation Harbors Actionable Driver Alterations: Survey of a Cancer Genomic Database and Review of Literature.

Introduction: Germline mutations are rare and have not been associated with increased risk of NSCLC.

Methods: We identified two sequential primary NSCLCs harboring distinct actionable driver alterations (EGFR E746 _S752 delinsV and ) in a patient with NSCLC with a novel germline mutation S5fs∗54 (c.14_20delCGGATGT).

Spotlight on Tepotinib and Capmatinib for Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation.

Mesenchymal-epithelial transition (MET) receptor tyrosine kinase is overexpressed, amplified, or mutated in 1-20% of NSCLC. MET dysregulation is associated with a poor prognosis. Recently, development of targeted therapies against MET exon 14 mutations has demonstrated efficacy and tolerability in early trials.

Deconstructing ADAURA: It is Time to Forgo Adjuvant Platinum-Based Chemotherapy in Resected IB-IIIA NSCLC (Except with Alterations?) When Adopting Adjuvant Osimertinib.

Adjuvant cisplatin-based chemotherapy is considered the standard of care for resected stage IB (tumor ≥ 4m)-IIIA non-small cell lung cancer (NSCLC). The ADAURA trial is a randomized placebo-controlled Phase III trial that demonstrated statistically significant improved disease-free survival (DFS) with the use of 3-years of adjuvant osimertinib in resected stage IB-IIIA NSCLC harboring epidermal growth factor receptor () del 19 or L858R mutations. Subgroup analysis revealed that the DFS improvement with adjuvant osimertinib is independent of adjuvant chemotherapy in the primary analysis.

Utility of tumor-informed circulating tumor DNA in the clinical management of gastrointestinal malignancies.

Background: Gastrointestinal (GI) malignancies represent a heterogeneous group of diseases. Traditional tumor markers, though part of standard-of-care, lack sensitivity and specificity. Tumor-informed circulating tumor DNA (ctDNA) assay-based molecular residual disease assessment as well as recurrence and treatment response monitoring can serve as a robust tool in patients with wide range of GI malignancies and ethnicities.

Amivantamab (JNJ-61186372) induces clinical, biochemical, molecular, and radiographic response in a treatment-refractory NSCLC patient harboring amplified triple EGFR mutations (L858R/ T790M/G796S) in cis.

The sequential use of 1-/2-generation to 3-generation epidermal growth factor (EGFR) tyrosine kinase inhibitors (TKIs) has led to the emergence of triple EGFR mutations generally consisting of the founder mutation (del 19 or L858R), gatekeeper mutation (T790M) and mutation (C797S) that abolishes the covalent binding of osimertinib to the EGFR protein (i.e., del 19 or L858R/T790M/C797S).

Spotlight on Sotorasib (AMG 510) for Positive Non-Small Cell Lung Cancer.

Mutations in codon 12 of have been identified in 13% of non-small cell lung cancer patients. Developing targeted therapies against mutation has proven to be challenging due to the abundance of GTP in the cytoplasm, rapid hydrolysis of GTP, and difficulty designing small molecules to achieve sufficient concentration for inhibition. Based on promising results in both preclinical and clinical trials, sotorasib, a novel inhibitor, was given conditional approval by the FDA in May 2021.

Identification of Novel α and Fusions in NSCLC Plus Additional Novel Fusions in Other Solid Tumors by Whole Transcriptome Sequencing.

Introduction: A novel fusion has recently been identified in NSCLC. We surveyed a large tumor database comprehensively profiled by whole transcriptome sequencing to investigate the incidence and distribution of fusions among various solid tumors.

Methods: Tumor samples submitted for clinical molecular profiling at Caris Life Sciences (Phoenix, AZ) that underwent whole transcriptome sequencing (NovaSeq [Illumina, San Diego, CA]) were retrospectively analyzed for fusion events.

Spotlight on Mobocertinib (TAK-788) in NSCLC with Exon 20 Insertion Mutations.

The exon 20 insertion (ex20ins) mutations are the third most common mutations seen in non-small cell lung cancer (NSCLC). More than 50 variants of ex20ins mutations have been identified with A767_V769dupASV being the most common variant across multiple surveys. Treatment with currently available EGFR tyrosine kinase inhibitors (TKIs) including osimertinib is generally ineffective.

Going beneath the tip of the iceberg. Identifying and understanding EML4-ALK variants and TP53 mutations to optimize treatment of ALK fusion positive (ALK+) NSCLC.

Since the discovery of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) gene fusion in non-small cell lung carcinoma (NSCLC) in 2007, more than 10 EML4-ALK variants based on the exon breakpoints in EML4 have been identified. Unlike other receptor tyrosine kinase fusion positive NSCLC such as ROS1 or RET fusion, EML4-ALK is the dominant fusion variant in ALK+ NSCLC accounting for approximately 85 % of all fusion variants in ALK+ NSCLC. Currently, eight EML4-ALK variants are generally recognized with a number (1, 2, 3a/b, 4', 5a/b, 5', 7, 8) with EML4-ALK variants 1 and 3 being the two most common variants accounting for 75-80 % of the total EML4-ALK variants.

Thromboembolism in ALK+ and ROS1+ NSCLC patients: A systematic review and meta-analysis.

Introduction: Increased thromboembolism (TE) has been reported in ALK+ and ROS1+ non-small cell lung cancer (NSCLC).

Materials And Methods: Odds ratios (OR) and hazard ratios (HR) of TE were calculated from meta-analysis and time-to-event analysis respectively for either ALK+ or ROS1+ NSCLC patients.

Results: We identified eight studies (766 ALK+, 143 ROS1+, 2314 non-ALK+ and non-ROS1+ NSCLC patients) for the meta-analysis.

Medication Errors in Surgery: A Classification Taxonomy and a Pilot Study in Postcall Residents.

Introduction: The post-call state in postgraduate medical trainees is associated with impaired decision-making and increased medical errors. An association between post-call state and medication prescription errors for surgery residents is yet to be established. Our objective was to determine whether post-call state is associated with increased proportion of medication prescription errors committed by surgery residents in an academic hospital without a computerized physician order entry (CPOE) system.

A Case of Myeloid Sarcoma following Allogeneic HSCT Presenting as Localized Hip Pain.

Myeloid sarcoma is a rare variant of acute myeloid leukemia (AML) which presents as an extramedullary soft tissue mass. Due to the rarity of this disease, along with nonspecific presenting symptoms, diagnosis can be delayed or missed without a high index of suspicion. In this case, we discuss a patient diagnosed with AML relapse in the form of myeloid sarcoma two years after allogeneic hematopoietic stem cell transplant (alloHSCT) for myelodysplastic syndrome (MDS) with the initial presentation for back pain misdiagnosed as spinal stenosis.

Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma.

Purpose: The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM).

Methods: We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM.

Results: Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients.