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ROS1  rearrangement, identified in ~2% of non-small cell lung cancer (NSCLC), has defined a distinctive molecular subtype. Patients with  ROS1  fusion have been shown to be highly sensitive to treatment with crizotinib. However, the efficacy of crizotinib in NSCLC patients with double  ROS1  fusions remains to be elucidated. Here, we report a 40-year-old male diagnosed with stage IIIA lung adenocarcinoma. Two  ROS1  fusions [SDC4- ROS1  (EX2:EX32) and  ROS1 -GK (EX31:EX13)] were detected simultaneously in tumor tissue of this patient by next-generation sequencing. Crizotinib was administered, and the patient showed a partial response in lung lesions. Nevertheless, a brain lesion was found at 8 months after treatment. The slightly short duration of response may be related to the presence of  ROS1-GK  rearrangement. This case proved that patients with  SDC4-ROS1  and  ROS1-GK  fusions may be sensitive to crizotinib, but short progression-free survival of this case showed that the presence of ROS1-GK rearrangement may affect the efficacy of crizotinib. A large-scale investigation on the efficacy of  ROS1  inhibitors in patients with complex  ROS1  fusions should be conducted in the future.

Case Report: Detection of Double ROS1 Translocations, SDC4-ROS1 and ROS1-GK, in a Lung Adenocarcinoma Patient and Response to Crizotinib