Humanistic burden of living with anaplastic lymphoma kinase-positive non-small-cell lung cancer: findings from the ALKConnect patient insight network and research platform

ALKConnect demonstrated that disease progression, HRQoL, fatigue/sleep, ALK TKIs and employment matter in ALK+ NSCLC. READ ARTICLE

Lung Cancer Management DOI: 10.2217/lmt-2020-0018

Authors: Lin HM, Pan X, Biller A, J Covey K, Huang H, Sugarman R, Scipione F, West H.

Case StudyKirk SmithNovember 20, 2020ctDNA, ALK, liquid biopsy, next-generation sequencing (NGS)

Next-generation sequencing to dynamically detect mechanisms of resistance to ALK inhibitors in ALK-positive NSCLC patients: a case report

Tyrosine kinase inhibitors (TKIs) of the anaplastic lymphoma kinase gene (ALK) have significantly improved the quality of life and survival of non-small cell lung cancer (NSCLC) patients whose tumors harbor an ALK translocation. However, most of these patients relapse within 2 to 3 years as the tumor acquires resistance mutations. Unlike beaming and digital PCR (dPCR), which only allow a few mutations to be analyzed, next-generation sequencing (NGS) approaches enable the simultaneous screening of multiple genetic alterations even when the frequencies of the variants are very low. We present the case of a 52-year-old man who was diagnosed with an ALK-positive NSCLC and was treated with crizotinib and, subsequently, ceritinib. The analysis of serial liquid biopsies by NGS detected two asynchronous mutations arising in the ALK locus during disease progression, namely p.Gly1269Ala (c.3806G>C) and p.Gly1202Arg (c.3604G>A), that conferred resistance to crizotinib and ceritinib, respectively...... READ ARTICLE

Translational Lung Cancer Research DOI:10.21037/tlcr.2020.02.07

Authors: Sánchez-Herrero E, Blanco Clemente M, Calvo V, Provencio M, Romero A.

Monitoring therapeutic response and resistance: analysis of circulating tumor DNA in patients with ALK+ lung cancer

Clinical utility of ctDNA was shown, both at pre-treatment by identifying a potential subgroup of ALK+ NSCLC patients who may derive more benefit from ensartinib and longitudinally by tracking resistance. Prospective application of this technology may translate to improved outcomes for NSCLC patients treated with ALK TKIs. READ ARTICLE

Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2019.08.003

Authors: Leora Horn MD, Jennifer G. Whisenant PhD, Heather Wakelee MD, Karen L. Reckamp MD, Huan Qiao, MD PhD, Ticiana A. Leal MD, Liping Du PhD, Jennifer Hernandez BS, Vincent Huang BS, George R. Blumenschein MD, Saiama N. Waqar MD, Sandip P. Patel MD, Jorge Nieva MD, Geoffrey R. Oxnard MD, Rachel E. Sanborn MD, Tristan Shaffer, Kavita Garg, Allison Holzhausen MS, Kimberly Harrow MBA, Chris Liang PhD, Lee P. Lim PhD, Mark Li, Christine M. Lovly MD, PhD

Pre-ClinicalKirk SmithAugust 22, 2019ctDNA, ALK, next-generation sequencing (NGS), liquid biopsy

Diagnostic accuracy of PCR for detecting ALK gene rearrangement in NSCLC patients: A systematic review and meta-analysis

NGS evaluation with the Oncomine Solid Tumour Fusion transcript kit and RT-PCR proved to have high sensitivity and specificity, advocating their use in routine practice. For maximal sensitivity and specificity, ALK status should be assessed by using two techniques and a third one in discordant cases. We therefore propose a customizable testing algorithm. These findings significantly influence existing testing paradigms and have clear clinical and economic impact. READ ARTICLE

Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2017.11.117

Authors: Igor Letovanec, Stephen Finn, Panagiota Zygoura, Paul Smyth, Alex Soltermann, Lukas Bubendorf, Ernst-Jan Speel, Antonio Marchetti, Daisuke Nonaka, Kim Monkhorst, Henrik Hager, Miguel Martorell, Aleksandra Sejda, Richard Cheney, Javier Hernandez-Losa, Eric Verbeken, Walter Weder, Spasenija Savic, Alessia Di Lorito, Atilio Navarro, Enriqueta Felip, Arne Warth, Paul Baas, Peter Meldgaard, Fiona Blackhall, Anne-Marie Dingemans, Hendrik Dienemann, Rafal Dziadziuszko, Johan Vansteenkiste, Cathal O'Brien, Thomas Geiger, Jon Sherlock, Jeoffrey Schageman, Urania Dafni, Roswitha Kammler, Keith Kerr, Erik Thunnissen, Rolf Stahel, Solange Peters, Rolf A. Stahel, Rafael Rosell, Fiona Blackhall, Urania Dafni, Keith M. Kerr, Miguel Ángel Molina, Lukas Bubendorf, Walter Weder, Erik Thunnissen, Solange Peters, Stephen Finn, Anita Hiltbrunner, Roswitha Kammler, Thomas Geiger, Nesa Marti, Urania Dafni, Zoi Tsourti, Varvara Polydoropoulou, Panagiota Zygoura, Stephen Finn, Paul Smyth, Cathal O’Brien, Steven Gray, Walter Weder, Alex Soltermann, Isabelle Opitz, Alessandra Curioni, Lukas Bubendorf, Spasenija Savic, Didier Lardinois, Anne-Marie Dingemans, Ernst-Jan M. Speel, Andrea Ruland, Antonio Marchetti, Alessia Di Lorito, Graziano De Luca, Sara Malatesta, Fiona Blackhall, Daisuke Nonaka, Anne Marie Quinn, Lynsey Franklin, Wojciech Biernat, Ania Wrona, Witold Rzyman, Jacek Jassem, Peter Meldgaard, Henrik Hager, Line B. Madsen, Carlos Camps, Miguel Martorell, Eloisa Jantus-Lewintre, Ricardo Guijarro, Keith M. Kerr, Marianne Nicolson, David A.J. Stevenson, William Mathieson, Paul Baas, Jeroen de Jong, Kim Monkhorst, Erik Thunnissen, Egbert Smit, Coralien van Setten, Joop de Langen, Enriqueta Felip, Javier Hernandez-Losa, Irene Sansano, Richard Cheney, Mary Beth Pine, Mary Reid, Elizabeth Taylor, Kristiaan Nackaerts, Christophe Dooms, Els Wauters, Sara Van Der Borght, Hendrik Dienemann, Thomas Muley, Arne Warth