ALK and ROS1 rearrangements, coexistence and treatment in epidermal growth factor receptor-wild type lung adenocarcinoma: a multicenter study of 732 cases

Background: Anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements represent two most frequent fusion targets in lung adenocarcinoma. Our study was intended to explore the clinicopathological characteristics, coexistence and treatment of ALK/ROS1-rearranged patients of lung adenocarcinoma without epidermal growth factor receptor (EGFR) mutation. Methods: Patients with wild-type EGFR mutation were screened for ALK/ROS1 at four domestic hospitals. ALK/ROS1 rearrangements were detected by reverse transcription-polymerase chain reaction (RT-PCR). Progression-free survival (PFS) curve was plotted with the Kaplan-Meier method. Results: Among 732 eligible cases, ALK and ROS1 rearrangements were detected in 89 (12.2%) and 32 (4.4%) patients respectively. One patient harbored coexisting ALK/ROS1 fusion. Both ALK and ROS1- positive phenotypes were predominantly detected in younger non-smokers. More ALK/ROS1-rearranged patients were correlated with the expressions of TTF1, napsin A and solid predominant adenocarcinoma subtype. Thirty-three ALK and six ROS1 rearrangement patients received crizotinib treatment at an advanced stage. The median PFS was 9.5 months for ALK-positive patients and it was not attained in ROS1- rearranged counterparts. Conclusions: The frequency of ALK and ROS1 rearrangements is elevated in EGFR-wild-type patients and the phenomenon of coexisting ALK/ROS1 has remained extremely rare. The rearrangements of ALK/ ROS1 are correlated with age, smoking status, expressions of TTF1 & napsin A and solid predominant adenocarcinoma subtype.