Non-small cell lung cancer (NSCLC) patients with ALK rearrangements are routinely treated with tyrosine kinase inhibitors (TKIs), leading to improved survival. However, clinical courses vary widely and the disease remains incurable. Therefore, early detection and molecular characterization of treatment failure is important for therapy guidance. To identify indicators of therapy response and resistance, we performed genotyping of circulating cell-free DNA (cfDNA), including panel-based deep sequencing (>4,200x coverage) and shallow whole-genome sequencing (sWGS; 0.5x coverage) from serial plasma samples (n=282) of 73 patients with ALK rearrangements. Variable mutation levels were marked in all patients and correlated with clinical features. At progression, individual dynamics of resistance mutations were seen: while some mutations became undetectable upon therapy switch, variant fractions of other alterations further increased. We also found mutated TP53 at the time of progression in pa..... READ ARTICLE
Clinical Cancer Research DOI:10.1158/1557-3265.LiqBiop20-A21
Authors: Steffen Dietz, Petros Christopoulos, Lisa Gu, Volker Endris, Zhao Yuan, Simon J. Ogrodnik, Tomasz Zemojtel, Marc A. Schneider, Anna-Lena Volckmar, Michael Meister, Thomas Muley, Martin Reck, Matthias Schlesner, Michael Thomas, Albrecht Stenzinger, Holger Sültmann.
