4.6 Article

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

Journal

FRONTIERS IN MEDICINE
Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmed.2021.649177

Keywords

next-generation sequencing; lung adenocarcinoma; double ROS1 fusion; crizotinib; novel ROS1 fusion

Funding

  1. Wu Jiping Medical Foundation [320.6750.16228]

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This case report highlights a NSCLC patient with dual ROS1 fusions SDC4-ROS1 and ROS1-GK, who showed partial response to crizotinib but developed a brain lesion possibly related to ROS1-GK rearrangement. Further large-scale investigations are needed to evaluate the efficacy of ROS1 inhibitors in patients with complex ROS1 fusions.
ROS1 rearrangement, identified in similar to 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.

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