Targeted Next-Generation Sequencing Analysis Predicts the Recurrence in Resected Lung Adenocarcinoma Harboring EGFR Mutations

Abstract

Simple Summary Despite complete resection and adjuvant chemotherapy, the recurrence rate of early EGFR-mutated lung adenocarcinoma remains high. We hypothesized that patients with recurrence-related genetic alterations would have poor prognosis and analyzed the genetic profiles of 131 patients using next-generation sequencing (NGS) with a 207 cancer-related gene panel. As a result, we revealed several negative prognostic factors for recurrence, such as a large number of concomitant mutations and the existence of specific mutation subtypes. Targeted NGS analysis provides information on the prognosis of patients with resected EGFR-mutation lung adenocarcinoma and helps to identify patients with high relapse risks who require intensive chemotherapy or adjuvant EGFR-TKIs treatments. Abstract Targeted NGS, widely applied to identify driver oncogenes in advanced lung adenocarcinoma, may also be applied to resected early stage cancers. We investigated resected EGFR-mutated lung adenocarcinoma mutation profiles to evaluate prognostic impacts. Tissues from 131 patients who had complete resection of stage I–IIIA EGFR-mutated lung adenocarcinoma were analyzed by targeted NGS for 207 cancer-related genes. Recurrence free survival (RFS) was estimated according to genetic alterations using the Kaplan–Meier method and Cox proportional regression analysis. The relapse rate was 25.2% (33/131). Five-year RFS of stages IA, IB, II, and IIIA were 82%, 75%, 35%, and 0%, respectively (p < 0.001). RFS decreased with the number of co-mutations (p = 0.025). Among co-mutations, the CTNNB1 mutation was associated with short RFS in a multivariate analysis (hazard ratio: 5.4, 95% confidence interval: 2.1–14.4; p = 0.001). TP53 mutations were associated with short RFS in stage IB–IIIA (p = 0.01). RFS was shorter with EGFR exon 19 deletion (19-del) than with mutation 21-L858R in stage IB–IIIA tumors (p = 0.008). Among 19-del subtypes, pL747_P753delinS (6/56, 8.9%) had shorter RFS than pE746_A750del (39/56, 69.6%), the most frequent subtype (p = 0.004).