1. High Prevalence of Concomitant Oncogene Mutations in Prospectively Identified Patients with ROS1-Positive Metastatic Lung Cancer 
Marcel Wiesweg, MD, Wilfried E.E. Eberhardt, MD, Henning Reis, MD, Saskia Ting, MD, Nikoleta Savvidou, Charlotte Skiba, Thomas Herold, PhD, Daniel C. Christoph, MD, Johannes Meiler, MD, Karl Worm, PhD, Stefan Kasper, MD, Dirk Theegarten, MD, Jörg Hense, MD, Thomas Hager, MD, Kaid Darwiche, MD, Filiz Oezkan, MD, Clemens Aigner, MD, Stefan Welter, MD, Hilmar Kühl, MD, Martin Stuschke, MD, Kurt W. Schmid, MD, Martin Schuler, MD 
Journal of Thoracic Oncology 
Volume 12, Issue 1, Pages (January 2017)
DOI: /j.jtho
Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

2. Figure 1
ROS1 fluorescence in situ hybridization (FISH), immunohistochemical (IHC) analysis, and histomorphological analysis (hematoxylin and eosin staining). (Upper panel) Photomicrographs of representative cases of pulmonary adenocarcinoma (ADC) of the different groups in standard staining (hematoxylin and eosin; original magnification, ×200 [top]), ROS1 IHC analysis (original magnification, ×200 [middle]), and ROS1 FISH (original magnification, ×1000 [bottom]). (I) ADC at metastatic site exhibiting single-cell ROS1 immunostaining but constant fusion signals in ROS1 FISH analysis. (II) ADC with pronounced atypia exhibiting faint but readily detectable ROS1 immunostaing with some split signals in FISH analysis. However, most nuclei display fused or very closely situated signals. (III) ADC exhibiting mostly papillary and solid histomorphological features and a distinct ROS1 IHC analysis staining result. FISH analysis revealed several split signals and also isolated green signals indicating ROS1 rearrangement. (Lower panel) Distribution of the percentage of ROS1 FISH–positive events. Results from the same patient at repeated analyses are connected by a dashed line. Patients with concomitant mutations are highlighted in red. Assignment into three groups: (I) 5% or less, (II) 10% to 30%, and (III) at least 50% FISH-positive events.
Journal of Thoracic Oncology  , 54-64DOI: ( /j.jtho )
Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

3. Figure 2
Survival of patients with ROS1-positive lung cancer. (A) Overall survival of patients with ROS1-positive (immunohistochemical analysis) lung cancer (n = 25, [green] median = 104 months, hazard ratio = 0.47), patients with EGFR-mutated lung cancer (n = 29 [yellow], p = 0.94, median = 49.2 months, hazard ratio = 0.49), and a control cohort of EGFR/anaplastic lymphoma kinase (ALK)/ROS1–negative lung cancer cases (n = 261 [blue], p = 0.044, median = 24.4 months) identified within the same time frame and biomarker screening program. (B) Overall survival of patients with ROS1-positive (≥15% positive fluorescence in situ hybridization events) lung cancer (n = 11 [green], median = 104 months, hazard ratio = 0.247) and a control cohort of EGFR/ALK/ROS1-negative lung cancer cases (n = 261 [blue], p = 0.036) identified within the same time frame and biomarker screening program. (C) Overall survival of patients with ROS1-positive (immunohistochemical analysis) lung cancer from initiation of pemetrexed-based chemotherapy (any line, n = 13 [green], median = 90.2 months, hazard ratio = 0.327) as compared with pemetrexed-treated (any line) patients with EGFR-mutated lung cancer (n = 17 [yellow], p = 0.47, median = 22.5 months, hazard ratio = 0.474), and pemetrexed-treated (any line) patients with EGFR/ALK/ROS1-negative lung cancer (n = 169 [blue], p = 0.01, median = 15.1 months).
Journal of Thoracic Oncology  , 54-64DOI: ( /j.jtho )
Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

4. Figure 3
Response to pemetrexed-based and crizotinib-based therapy in a patient with ROS1-positive metastatic lung cancer. Representative computed tomography images and positron emission tomography/computed tomography fusion images of a patient (identifier 11) with ROS1-positive (25% positive events at fluorescence in situ hybridization) lung cancer obtained before initiation of cisplatin/pemetrexed (A), after 54 months of pemetrexed maintenance therapy (B), at multilocular progression after a treatment holiday (C), and after 12 weeks of crizotinib (D).
Journal of Thoracic Oncology  , 54-64DOI: ( /j.jtho )
Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions