Different Clinicopathologic and Computed Tomography Imaging Characteristics of Primary and Acquired EGFR T790M Mutations in Patients with Non-Small-Cell Lung Cancer

Abstract

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

Acknowledgments

This work was supported by the National Key R&D Program of China (No. 2017YFC1308700), CAMS Innovation Fund for Medical Sciences (No. 2017-I2M-1-005, 2019-I2M-2-002), National Natural Science Foundation of China (No. 81771830), and Beijing Municipal Science and Technology Project (No. Z201100005620002).

Abbreviations

ARMS, amplification refractory mutation system; AUC, area under the receiver operating characteristic curve; ctDNA, circulating tumor DNA; CT, computed tomography; DCA, decision curve analysis; EBUS, endobronchial ultrasound; EGFR, epidermal growth factor receptor; FDG, fluorodeoxyglucose; GGO, ground-glass opacity; NGS, next-generation sequencing; NSCLC, non-small-cell lung cancer; OR, odds ratio; PACS, picture archiving and communication system; PFS, progression-free survival; TKIs, tyrosine kinase inhibitors.

Data Sharing Statement

The data and material are available from the corresponding author (Shijun Zhao) upon reasonable request.

Ethics Statement

This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Ethics Committee of the Cancer Hospital, Chinese Academy of Medical Sciences (No. NCC2017ZDY-03); written informed consent was waived due to anonymous data analysis.

Disclosure

The authors report no conflicts of interest in this work.