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Rearranged during transfection proto-oncogene ( RET ) fusions represent a potentially targetable oncogenic driver in non-small cell lung cancer (NSCLC). Imaging features and metastatic patterns of advanced RET fusion-positive ( RET +) NSCLC are not well established. Our goal was to compare the imaging features and patterns of metastases in RET +, ALK + and ROS1 + NSCLC. Patients with RET +, ALK +, or ROS1 + NSCLC seen at our institution between January 2014 and December 2018 with available pre-treatment imaging were identified. The clinicopathologic features, imaging characteristics, and the distribution of metastases were reviewed and compared. We identified 215 patients with NSCLC harboring RET , ALK , or ROS1 gene fusion ( RET = 32; ALK = 116; ROS1 = 67). Patients with RET + NSCLC were older at presentation compared to ALK + and ROS1 + patients (median age: RET = 64 years; ALK = 51 years, p &lt; 0.001; ROS = 54 years, p = 0.042) and had a higher frequency of neuroendocrine histology ( RET = 12%; ALK = 2%, p = 0.025; ROS1 = 0%, p = 0.010). Primary tumors in RET + patients were more likely to be peripheral ( RET = 69%; ALK = 47%, p = 0.029; ROS1 = 36%, p = 0.003), whereas lobar location, size, and density were comparable across the three groups. RET + NSCLC was associated with a higher frequency of brain metastases at diagnosis compared to ROS1 + NSCLC ( RET = 32%, ROS1 = 10%; p = 0.039. Metastatic patterns were otherwise similar across the three molecular subgroups, with high incidences of lymphangitic carcinomatosis, pleural metastases, and sclerotic bone metastases. RET + NSCLC shares several distinct radiologic features and metastatic spread with ALK + and ROS1+ NSCLC. These features may suggest the presence of RET fusions and help identify patients who may benefit from further molecular genotyping.

Imaging Features and Patterns of Metastasis in Non-Small Cell Lung Cancer with RET Rearrangements