The Impact of EGFR Tyrosine Kinase Inhibitor on the Natural Course of Concurrent Subsolid Nodules in Patients with Non-Small Cell Lung Cancer.

Purpose The role of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non-small-cell lung cancer (NSCLC). Material and Methods Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cut-off value of 2mm; increase (≥ 2mm), decrease (≤ -2mm) and no change (-2mm < size change < +2mm). Results A total of 77 SSNs, 51 (66.2%) pure ground-glass and 26 (33.8%) part-solid nodules, were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio: 4.29, 95% confidence interval [1.21-15.29], p=0.025). Conclusion Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.