Abstract 5896: Targeted NGS analysis to predict recurrence in resected EGFR- mutated lung adenocarcinoma
Authors: Kim In Ae , Kim Hee Jung , Hur Jae Young , Lee Seung En , Park Jung Hoon , Lee Song Am , Hwang Jae Jun , Kim Wan Seop , Lee Kye Young 
Published: September 2020

Background: Targeted next-generation sequencing (NGS) is widely applied in personalized therapy of NSCLC patients by identifying driver oncogenes. Another important application of targeted NGS analysis is to predict recurrence in resected early stage NSCLC patients. We investigated targeted NGS analysis to identify the genetic alterations related to the recurrence in resected EGFR-mutated lung adenocarcinoma.

Methods: Tissues from 130 patients who had complete resection of stage I to IIIA EGFR mutated adenocarcinoma (median follow-up: 45 months), were analyzed by targeted NGS with 170 cancer-related genes. The DFS according to the numbers and types of gene alterations were estimated using the Kaplan-Meier method. The independent biomarkers related to recurrence were identified by Cox proportional hazard regression analysis.

Results: The relapses after surgical resections were observed in 32 patients of 130 (24.6%). The relapses were associated not with sex and smoking history but with visceral-pleural invasion (p=0.001), lympho-vascular invasion (p=0.002), and stage(p=0.001). Relapse rates were increased in order by L858R (11/59, 18.6%), exon 19 deletion (16/56, 28.6%), compound EGFR mutation (3/10, 30%) and exon 20 mutation (2/5, 40%), but there was no statistical difference. 13 of 16 (81%) relapse patients with 19 deletion had E746_A750 del. It indicates that the hot spot of exon 19 deletion related to recurrence is E746_A750 del. In the aspect of the number of mutations, the patients with single mutation were 68(51.5%). 44(33.8%) had dual mutation, 13(10.8%) had triple mutation. DFS was associated with the number of genetic mutations (p=0.025). The 5-year DFS rates were 83%, 62% and 25% for single, dual and triple mutation respectively(p&lt;0.001). Besides, we found the CTNNB1 mutation was associated with worse DFS in a multivariate analysis adjusted by sex, age, stage, smoking history and operation methods (hazard ratio [HR]: 5.4, 95% confidence interval: 2.1-14.4; p=0.001). The patients with CTNNB1/EGFR co-mutation were expected to have shorter DFS than the patients with single EGFR mutation (p=0.003).

Conclusions: The number of co-occurring mutations, CTNNB1 mutation and del E746_A750 in exon19 was negative prognostic factors for DFS in resected EGFR-mutated lung adenocarcinoma. We recommend that the targeted NGS should be performed to identify the genetic alterations so we can predict the outcome and plan adjuvant chemotherapy or EGFR tyrosine kinase inhibitor therapy to patients with a higher risk of recurrence.

Citation Format: In Ae Kim, Hee Jung Kim, Jae Young Hur, Seung En Lee, Jung Hoon Park, Song Am Lee, Jae Jun Hwang, Wan Seop Kim, Kye Young Lee. Targeted NGS analysis to predict recurrence in resected EGFR- mutated lung adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5896.