Clinical and Radiological Characteristics to Differentiate Between EGFR Exon 21 and Exon 19 Mutations in Patients With Lung Adenocarcinoma: A Systematic Literature Review and Meta-Analysis

Epidermal Growth Factor Receptor (EGFR) mutations in lung adenocarcinoma have been previously associated with specific clinical characteristics and Computed Tomography (CT) patterns. However, associations among individual EGFR mutations have not been evaluated. We aim to differentiate if the most common EGFR mutations (exon 21 and 19) are related to specific clinical characteristics or CT patterns. A systematic review and meta-analysis of 5 databases were conducted with literature from January 2002 to July 2021. Eligible studies were of an experimental or observational design that included lung adenocarcinoma patients with confirmed EGFR exon mutations (21 and 19) and associated clinical characteristics and CT imaging patterns. Quality was assessed using the QUADAS-2 tool. The association between clinical and CT patterns and EGFR exon mutations 21 and 19 was evaluated using odds ratios (OR) and then pooled and analyzed with a fixed or random-effects model. This study follows the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. A total of 12 retrospective diagnostic accuracy studies were included. Pooled analysis showed that characteristics such as absence of smoking status (OR 1.29 [95% CI 0.97 - 1.70]), and female sex (OR 1.23 [95% CI 0.83 - 1.82]); and CT patterns such as Ground Glass Opacities (GGO) (OR 1.03 [95% CI 0.78 -1.34]), air bronchogram (OR 0.78 [95% CI 0.44 -1.39]), pleural retraction (OR 0.83 [95% CI 0.53 - 1.28]), and spiculation (OR 0.80 [95% CI 0.48 - 1.31]) were not significantly associated to a specific mutation. Specific EGFR exon 21 and 19 mutations cannot be differentiated through characteristics (absence of smoking status and female sex) or radiological patterns (GGO, air bronchogram, pleural retraction, and speculation). There is limited data to assess if early disease stage or vascular convergence aids in differentiating exon 21 from 19 mutations in patients with lung adenocarcinoma.