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ROS1 rearrangements in lung adenocarcinoma: prognostic impact,therapeutic options and genetic variability
Authors:Matthias Scheffler  Anne Schultheis  Cristina Teixido  Sebastian Michels  Daniela Morales-Espinosa  Santiago Viteri  Wolfgang Hartmann  Sabine Merkelbach-Bruse  Rieke Fischer  Hans-Ulrich Schildhaus  Jana Fassunke  Martin Sebastian  Monika Serke  Britta Kaminsky  Winfried Randerath  Ulrich Gerigk  Yon-Dschun Ko  Stefan Krüger  Roland Schnell  Achim Rothe  Cornelia Kropf-Sanchen  Lukas Heukamp  Rafael Rosell  Reinhard Büttner  Jürgen Wolf
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.

Patients and 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.

Conclusion

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.
Keywords:non-small cell lung cancer   ROS1   prognosis   chemotherapy   lung cancer
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