Performance of an RNA-Based Next-Generation Sequencing Assay for Combined Detection of Clinically Actionable Fusions and Hotspot Mutations in NSCLC

Introduction: With its expanding list of approved and emerging therapeutic indications, NSCLC is the exemplar tumor type requiring upfront assessment of several biomarkers to guide clinical management. Next-generation sequencing allows identification of different types of molecular alterations, each with specific analytical challenges. Library preparation using parallel DNA and RNA workflows can overcome most of them, but it increases complexity of laboratory operations, turnaround time, and costs. We describe the performance characteristics of a 15-gene RNA panel on the basis of anchored multiplex polymerase chain reaction for combined detection of clinically relevant oncogenic fusion transcripts and hotspot small variants... Conclusions: This ultrafocused RNA–next-generation sequencing assay offers an advantageous option with single unified workflow for simultaneous detection of clinically relevant hotspot mutations and fusions in NSCLC, focusing on actionable gene targets. READ ARTICLE

JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2022.100276

Authors: Patrice Desmeules, Dominique K. Boudreau, Nathalie Bastien, Marie-Chloé Boulanger, Yohan Bossé, Philippe Joubert, Christian Couture

Intergenic Breakpoints Identified by DNA Sequencing Confound Targetable Kinase Fusion Detection in NSCLC

Introduction: Next-generation sequencing (NGS) based on genomic DNA has been widely applied for gene rearrangement detection in patients with NSCLC. However, intergenic-breakpoint fusions, in which one or both genomic breakpoints localize to intergenic regions, confound kinase fusion detection. We evaluated the function of intergenic-breakpoint fusions with multiplex molecular testing approaches... Conclusions: Intergenic-breakpoint fusions detected by DNA sequencing confound kinase fusion detection in NSCLC, as functional fusion transcripts may be generated or not. Additional validation testing using RNA/protein assay should be performed in intergenic-breakpoint fusion cases to guide optimal treatment. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2020.02.023

Authors: Weihua Li, Yutao Liu, Wenbin Li, Li Chen, Jianming Ying

Anaplastic Lymphoma Kinase Mutation–Positive Non–Small Cell Lung Cancer

KEY POINTS:
Non–small cell lung cancer with anaplastic lymphoma kinase (ALK) chromosomal rearrangement is
sensitive to treatment with tyrosine kinase inhibitors (TKIs).
Numerous TKIs have been developed in recent years, including alectinib, which is the current
preferred first-line agent for treatment-naı¨ve patients.
The development of resistance has led to next-generation ALK inhibitors that better penetrate the
central nervous system, which has improved the treatment of brain metastasis. READ ARTICLE

Thoracic Surgery Clinics DOI:10.1016/j.thorsurg.2019.12.001

Authors: Anthony V. Serritella, Christine M. Bestvina

Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer

Lung cancer is the leading cause of cancer
mortality. It is classified into different histologic subtypes, including adenocarcinoma, squamous carcinoma, and large cell carcinoma (commonly referred as non–small cell lung cancer) and small cell lung cancer. Comprehensive molecular characterization of lung cancer has expanded our understanding of the cellular origins and molecular pathways affected in each of these subtypes. Many of these genetic alterations represent potential therapeutic targets for which drugs are constantly under development. This article discusses the molecular characteristics of the main lung cancer subtypes and discusses the current guidelines and novel targeted therapies, including checkpoint immunotherapy. READ ARTICLE

Surgical Pathology Clinics DOI:10.1016/j.path.2019.11.002

Authors: Roberto Ruiz-Cordero, Walter Patrick Devine

Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations

Background: A retrospective analysis verified the role of gene mutations in brain metastasis in patients with non-small cell lung cancer (NSCLC). Conclusions: An EGFR mutation, ALK gene fusion, and RET gene fusion in advanced NSCLC patients play roles in brain metastasis as positive driver genes. Impact: An EGFR mutation, and ALK and RET gene fusions are risk factors for brain metastasis in advanced NSCLC patients. READ ARTICLE

Cancer Medicine. DOI: 10.1002/cam4.2706

Authors: Huijuan Wang, Ziqi Wang, Guowei Zhang, Mina Zhang, Xiaojuan Zhang, Haixia Li, Xuanxuan Zheng, Zhiyong Ma

Definition of Synchronous Oligometastatic Non–Small Cell Lung Cancer—A Consensus Report

Introduction: Improved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process. Conclusion: A multidisciplinary consensus statement on the definition and staging of sOM NSCLC has been formulated. This statement will help to standardize inclusion criteria in future clinical trials. READ ARTICLE

Journal of Thoracic Oncology. DOI: 10.1016/j.jtho.2019.07.025

Authors: Anne-Marie C. Dingemans, Lizza E.L. Hendriks, Thierry Berghmans, Antonin Levy, Baktiar Hasan, Corinne Faivre-Finn, Matteo Giaj-Levra, Niccolò Giaj-Levra, Nicolas Girard, Laurent Greillier, Sylvie Lantuéjoul, John Edwards, Mary O’Brien, Martin Reck, Egbert F. Smit, Paul Van Schil, Pieter E. Postmus, Sara Ramella, Yolande Lievens, Mina Gaga, Nir Peled, Giorgio V. Scagliotti, Suresh Senan, Luiz Paz-Ares, Matthias Guckenberger, Fiona McDonald, Simon Ekman, Tanja Cufer, Hester Gietema, Maurizio Infante, Rafal Dziadziuszko, Solange Peters, Ramon Rami Porta, Johan Vansteenkiste, Christophe Dooms, Dirk de Ruysscher, Benjamin Besse, Silvia Novello