LAUSR

Objectives: To describe the radiological phenotype of HER2-mutant lung cancers on CT at presentation. Methods: Eligible patients with lung adenocarcinomas with HER2 mutations were stage-matched with two control groups (EGFR- and KRAS-mutant groups). Evaluated CT features of the primary tumor included size, location, consistency, contour, presence of pleural tags and pleural retractions. Presence of pleural effusions, lung metastases, adenopathy, chest wall invasion, and were also recorded. Wilcoxon rank-sum and Fisher's exact tests were used to compare continuous and categorical features, respectively. Results: One hundred and fifty-four patients were identified: 50 (33%) harbored HER2 mutations, 56 (36%) harbored KRAS mutations, and 48 (31%) harbored EGFR mutations. Compared with KRAS, HER2 tumors presented as smaller lesions (2.3 cm versus 2.9 cm, p = 0.005 for length; 1.6 cm versus 2.1 cm, p = 0.002 for width) with the presence of pleural tags (74% vs. 52%, p = 0.03), pleural retractions (58% vs. 39%, p = 0.006), ipsilateral hilar (36% vs. 16%, p = 0.03) and scalene/supraclavicular N3 adenopathy (24% vs. 7%, p = 0.03). Compared with EGFR, pleural retractions were more prevalent among the HER2 tumors (58% vs. 37%, p = 0.05). Conclusions: Lung adenocarcinomas with HER2 gene mutation exhibit an aggressive behavior manifesting by higher incidence of local invasion, compared to KRAS and EGFR mutant controls, and a nodal metastatic spread compared to KRAS-mutant control. This is the first radiogenomics study of HER2 mutations in lung cancer.