Genomic profiling of NSCLC tumors with the TruSight oncology 500 assay provides broad coverage of clinically actionable genomic alterations and detection of known and novel associations between genomic alterations, TMB, and PD-L1.

Introduction: Matching patients to an effective targeted therapy or immunotherapy is a challenge for advanced and metastatic non-small cell lung cancer (NSCLC), especially when relying on assays that test one marker at a time. Unlike traditional single marker tests, comprehensive genomic profiling (CGP) can simultaneously assess NSCLC tumors for hundreds of genomic biomarkers and markers for immunotherapy response, leading to quicker and more precise matches to therapeutics.

Methods: In this study, we performed CGP on 7,606 patients with advanced or metastatic NSCLC using the Illumina TruSight Oncology 500 (TSO 500) CGP assay to show its coverage and utility in detecting known and novel features of NSCLC.

Brief Report: Methylation-Based ctDNA Serial Monitoring Correlates With Immunotherapy Response in NSCLC.

Purpose: Circulating tumor DNA (ctDNA) can reflect the genetic and epigenetic composition of malignancies and can serve as a noninvasive biomarker for cancer diagnostics and monitoring. This study aimed to evaluate the utility of a methylation-based ctDNA assay as a predictive tool in non-small cell lung cancer (NSCLC) anti-PD1 based immunotherapy monitoring.

Methods: We evaluated a cohort of 20 patients with NSCLC treated with anti-PD1 based immunotherapy that had both baseline and follow-up blood draws as well as outcome data available.

Efficacy and tolerability of osimertinib with dabrafenib and trametinib in V600E acquired -mutant non-small cell lung cancer: a case series.

Background: Acquired mutations within bypass pathways including V600E have been observed in post-osimertinib progression in -mutant non-small cell lung cancer (NSCLC). The combination of dabrafenib and trametinib is currently Food and Drug Administration-approved in V600E-mutant NSCLC. However, the application of osimertinib and dabrafenib and trametinib in the setting of acquired V600E mutation resistance from osimertinib therapy has not been clearly defined.

Proceedings of the 1st biannual bridging the gaps in lung cancer conference.

Lung cancer is the leading cause of cancer death in the US and globally. The mortality from lung cancer has been declining, due to a reduction in incidence and advances in treatment. Although recent success in developing targeted and immunotherapies for lung cancer has benefitted patients, it has also expanded the complexity of potential treatment options for health care providers.

Efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients with rare mutations: a real-world retrospective study.

Background: Kirsten rat sarcoma homolog () mutations are one of the key drivers in non-small cell lung cancer (NSCLC) and FDA-approved specific inhibitors of -G12C mutation are available clinically. However, inhibitors of certain KRAS mutation subtypes remain unavailable, especially rare mutations including G13C, G13D, and Q61H. In this study, we retrospectively investigated the outcomes of NSCLC patients with rare -mutation to determine if they may benefit from immune checkpoint inhibitors (ICIs).

Adagrasib Treatment After Sotorasib-Related Hepatotoxicity in Patients With -Mutated Non-Small Cell Lung Cancer: A Case Series and Literature Review.

Purpose: is the most commonly mutated driver oncogene in non-small cell lung cancer (NSCLC). Sotorasib and adagrasib, KRAS inhibitors, have been granted accelerated US approval; however, hepatotoxicity is a common side effect with higher rates in patients treated with sotorasib proximal to checkpoint inhibitor (CPI) therapy. The aim of this study was to assess the feasibility and safety of adagrasib after discontinuation of sotorasib because of treatment-related grade 3 hepatotoxicity through real-world and clinical cases.

Measurement of ctDNA Tumor Fraction Identifies Informative Negative Liquid Biopsy Results and Informs Value of Tissue Confirmation.

Purpose: Liquid biopsy (LBx) for tumor profiling is increasingly used, but concerns remain regarding negative results. A lack of results may truly reflect tumor genomics, or it may be a false negative that would be clarified by tissue testing. A method of distinguishing between these scenarios could help clarify when follow-on tissue testing is valuable.

The optimal time for endotracheal intubation in subjects with coronavirus disease 2019 pneumonia: A retrospective observational study.

Background: The optimal timing of intubation has been debated among healthcare professionals, current studies do not show any differences between early and late intubation. most studies failed to show any significant difference in clinical outcomes between early or late intubation.

Methods: The study was conducted as a retrospective review of subjects with confirmed coronavirus disease 2019 admitted to the Dubai Hospital intensive care unit (ICU).

A bioinformatics analysis of potential cellular communication networks in non-alcoholic steatohepatitis and colorectal adenoma using scRNA-seq and bulk-seq.

Background: Non-alcoholic fatty liver disease (NAFLD) is the global most common chronic liver disease. Non-alcoholic steatohepatitis (NASH), an inflammatory subtype of NAFLD, has been shown to significantly increase the risk of colorectal adenoma (CRA). Therefore, from the perspective of bioinformatics analysis, the potential mechanisms of NASH/NAFLD-CRA can be explored.

Tumor Fraction Correlates With Detection of Actionable Variants Across > 23,000 Circulating Tumor DNA Samples.

Purpose: Profiling of circulating tumor DNA (ctDNA) is increasingly adopted in the management of solid tumors, concurrent with increased availability of more comprehensive ctDNA panels. However, variable ctDNA shed can result in variable assay sensitivity. We studied the relationship between ctDNA tumor fraction (TF) and detection of actionable alterations across cancer types.

The efficacy of anlotinib as third-line treatment for non-small cell lung cancer by EGFR mutation status: a subgroup analysis of the ALTER0303 randomized phase 3 study.

Background: Anlotinib demonstrated improved overall survival (OS) and progression-free survival (PFS) compared with placebo as a third-line or subsequent therapy in patients with non-small cell lung cancer (NSCLC) in the ALTER0303 trial. The status of epidermal growth factor receptor (EGFR) mutation, different previous treatment may affect the efficacy of subsequent therapy, and we did this subgroup analysis to characterize the efficacy of anlotinib in patients with and without EGFR mutation.

Methods: The ALTER0303 trial was a randomized, double-blind, phase 3 study of anlotinib in patients with NSCLC who failed at least 2 lines of treatment.

A phase 1b/2 study of PF-06747775 as monotherapy or in combination with Palbociclib in patients with epidermal growth factor receptor mutant advanced non-small cell lung cancer.

Introduction: This Phase 1/2 study (NCT02349633) explored the safety and antitumor activity of PF-06747775 (oral, third-generation epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor) in patients with advanced non-small cell lung cancer after progression on an EGFR inhibitor.

Methods: Phase 1 was a dose-escalation study of PF-06747775 monotherapy (starting dose: 25 mg once daily [QD]). Phase 1b/2 evaluated PF-06747775 monotherapy at recommended Phase 2 dose (RP2D; Cohort 1); PF-06747775 200 mg QD plus palbociclib (starting dose: 100 mg QD orally; Cohort 2A); and PF-06747775 monotherapy at RP2D in a Japanese lead-in cohort.

High-Dose Osimertinib for CNS Progression in EGFR+ NSCLC: A Multi-Institutional Experience.

Introduction: This multicenter review evaluated the efficacy and safety of osimertinib dose escalation for central nervous system (CNS) progression developing on osimertinib 80 mg in -mutant NSCLC.

Methods: Retrospective review identified 105 patients from eight institutions with advanced -mutant NSCLC treated with osimertinib 160 mg daily between October 2013 and January 2020. Radiographic responses were clinically assessed, and Kaplan-Meier analyses were used.

The relationship between different subtypes of and PD-L1 & tumor mutation burden (TMB) based on next-generation sequencing (NGS) detection in Chinese lung cancer patients.

Background: gene mutations are the most common driver oncogenes in non-small cell lung cancer (NSCLC). We conducted an analysis of the immunological characteristics including tumor mutation burden and programmed death-ligand 1 (PD-L1) expression of different subtypes of in 2880 -mutant NSCLC patients.

Methods: A total of 2,880 patients with NSCLC were included in the study.

Selective KRAS G12C inhibitors in non-small cell lung cancer: chemistry, concurrent pathway alterations, and clinical outcomes.

Cancers harboring mutations in the Kirsten rat sarcoma homolog (KRAS) gene have been associated with poor prognosis and lack of targeted therapies. KRAS mutations occur in approximately one in four patients diagnosed with non-small cell lung cancer (NSCLC) with KRAS G12C mutations harbored at approximately 11-16%. Research into KRAS-driven tumors and analytical chemistry have borne a new class of selective small molecules against the KRAS G12C isoform.

Usefulness of Circulating Tumor DNA in Identifying Somatic Mutations and Tracking Tumor Evolution in Patients With Non-small Cell Lung Cancer.

Background: The usefulness of circulating tumor DNA (ctDNA) in detecting mutations and monitoring treatment response has not been well studied beyond a few actionable biomarkers in non-small cell lung cancer (NSCLC).

Research Question: How does the usefulness of ctDNA analysis compare with that of solid tumor biopsy analysis in patients with NSCLC?

Methods: We retrospectively evaluated 370 adult patients with NSCLC treated at the City of Hope between November 2015 and August 2019 to assess the usefulness of ctDNA in mutation identification, survival, concordance with matched tissue samples in 32 genes, and tumor evolution.

Results: A total of 1,688 somatic mutations were detected in 473 ctDNA samples from 370 patients with NSCLC.

RNA Based Approaches to Profile Oncogenic Pathways From Low Quantity Samples to Drive Precision Oncology Strategies.

Precision treatment of cancer requires knowledge on active tumor driving signal transduction pathways to select the optimal effective targeted treatment. Currently only a subset of patients derive clinical benefit from mutation based targeted treatment, due to intrinsic and acquired drug resistance mechanisms. Phenotypic assays to identify the tumor driving pathway based on protein analysis are difficult to multiplex on routine pathology samples.

Applications of cell-free circulating tumor DNA detection in EGFR mutant lung cancer.

Analyses of cell-free tumor DNA (ctDNA) have provided a non-invasive strategy for cancer diagnosis, the identification of molecular aberrations for treatment identification, and evaluation of tumor response. Sensitive and specific ctDNA sequencing strategies have allowed for implementation into clinical practice for the initial genotyping of patients and resistance monitoring. The specific need for EGFR mutation detection for the management of lung cancer patients has been an early imperative and has set the stage for non-invasive molecular profiling across other oncogenic drivers.

Assessing tumor heterogeneity using ctDNA to predict and monitor therapeutic response in metastatic breast cancer.

Tumor heterogeneity was associated with treatment outcome of metastatic cancers but few studies have examined whether tumor heterogeneity in circulating tumor DNA (ctDNA) can be used to predict treatment outcome. ctDNA analysis was performed in 37 HER2-positive metastatic breast cancer patients treated with pyrotinib. Patients with high tumor heterogeneity had significantly worse PFS outcomes, with a median PFS of 30.