title: ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability.
abstract: BACKGROUND
  While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients.
  
  
  METHODS
  1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients.
  
  
  RESULTS
  19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations.
  
  
  CONCLUSIONS
  ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors: Matthias
authors: M
authors: Scheffler
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors: Anne
authors: A
authors: Schultheis
authors: Pangaea Biotech, Quirón Dexeus University Hospital, Barcelona, Spain.
authors: Cristina
authors: C
authors: Teixido
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors: Sebastian
authors: S
authors: Michels
authors: Institut d'Investigació en Ciències de la Salut, Germans Trias i Pujol, Badalona, Spain.
authors: Daniela
authors: D
authors: Morales-Espinosa
authors: Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona, Spain.
authors: Santiago
authors: S
authors: Viteri
authors: Gerhard-Domagk-Institute of Pathology, University Hospital of Münster, Münster, Germany.
authors: Wolfgang
authors: W
authors: Hartmann
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors: Sabine
authors: S
authors: Merkelbach-Bruse
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors: Rieke
authors: R
authors: Fischer
authors: Institute of Pathology, University Hospital of Göttingen, Göttingen, Germany.
authors: Hans-Ulrich
authors: HU
authors: Schildhaus
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors: Jana
authors: J
authors: Fassunke
authors: Department of Hematology/Oncology, University Hospital of Frankfurt, Frankfurt, Germany.
authors: Martin
authors: M
authors: Sebastian
authors: Department for Pulmonology and Thoracic Oncology, Lung Clinic Hemer, Hemer, Germany.
authors: Monika
authors: M
authors: Serke
authors: Clinic for Pneumology and Allergology Center for Sleep Medicine and Respiratory Care, Bethanien Hospital, Solingen, Germany.
authors: Britta
authors: B
authors: Kaminsky
authors: Clinic for Pneumology and Allergology Center for Sleep Medicine and Respiratory Care, Bethanien Hospital, Solingen, Germany.
authors: Winfried
authors: W
authors: Randerath
authors: Thoracic Centre, Malteser Hospital Bonn/Rhein-Sieg, Bonn, Germany.
authors: Ulrich
authors: U
authors: Gerigk
authors: Johanniter Hospital, Evangelical Clinics of Bonn, Bonn, Germany.
authors: Yon-Dschun
authors: YD
authors: Ko
authors: Clinic for Pneumology/Allergology/Sleep Medicine and Respiratory Care, Florence-Nightingale-Hospital, Düsseldorf, Germany.
authors: Stefan
authors: S
authors: Krüger
authors: Practice for Internistic Oncology and Hematology, Frechen, Germany.
authors: Roland
authors: R
authors: Schnell
authors: Practice for Hematology and Oncology Mainka/Dietze/Rothe, Cologne, Germany.
authors: Achim
authors: A
authors: Rothe
authors: Department II for Internal Medicine, University Hospital of Ulm, Ulm, Germany.
authors: Cornelia
authors: C
authors: Kropf-Sanchen
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors: Lukas
authors: L
authors: Heukamp
authors: Instituto Oncológico Dr Rosell, Quirón Dexeus University Hospital, Barcelona, Spain.|Cancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.|Molecular Oncology Research (MORe) Foundation, Barcelona, Spain.
authors: Rafael
authors: R
authors: Rosell
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors: Reinhard
authors: R
authors: Büttner
authors: Center for Integrated Oncology Köln Bonn, Cologne, Germany.|Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
authors: Jürgen
authors: J
authors: Wolf
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D005260:Female; D015321:Gene Rearrangement; D014644:Genetic Variation; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human
keywords: ROS1; chemotherapy; lung cancer; non-small cell lung cancer; prognosis