Purpose: Although patients with primary and acquired epidermal growth factor receptor (EGFR) T790M  positive non-small-cell lung cancer (NSCLC) respond to osimertinib treatment, the optimal treatment strategy differs for these two groups of patients. This study aimed to compare the clinicopathologic and computed tomography (CT) imaging characteristics between primary and acquired EGFR T790M  mutations in patients with NSCLC before treatment.
Patients and Methods: We enrolled two groups of patients with primary or acquired EGFR T790M  mutation NSCLC (n = 103 per group) from January 2012 to December 2019. We analyzed their clinicopathologic and CT characteristics and differences between the groups. The groups were further categorized based on 21L858R  and 19del  to exclude the effect of coexistent mutations.
Results: Primary, compared to acquired, T790M  mutation tends to coexist with 21L858R  (P < 0.001), exhibiting earlier tumor stage (P < 0.001), higher differentiation (P = 0.029), higher proportion of lepidic subtype adenocarcinoma (P < 0.001), and significant associations with some CT features (multiple primary lung cancers, ground-glass opacity, air bronchogram, and vacuole sign [all P < 0.001]). The combined model, composed of clinicopathologic and conventional CT signature and CT-radiomic signature, showed good discriminative ability with the area under the receiver operating characteristic curve 0.90 and 0.91 in the training and validation datasets, respectively. The T790M  mutation contributed to these differences independently of coexistent mutations.
Conclusion: We identified clinicopathologic and CT imaging differences between primary and acquired T790M  mutations. These findings provide insights into developing future personalized T790M  mutation status-based theranostic strategies.
Keywords: non-small-cell lung cancer, T790M mutation, osimertinib, clinicopathologic characteristic, computed tomography