Prognostic outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical epidermal growth factor receptor mutations

Author:

Chen Tao1,Wen Jialiang1,Li Yingze1,Deng Jiajun1,Zhong Yifan1,Hou Likun2,She Yunlang1,Xie Dong1ORCID,Chen Chang1ORCID

Affiliation:

1. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai, China

2. Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai, China

Abstract

Abstract OBJECTIVES Limited data exist on the characteristics of atypical epidermal growth factor receptor (EGFR) mutations in early-stage lung cancer. Our goal was to elucidate the associations with outcomes and recurrence patterns in resected stage I lung adenocarcinoma harbouring atypical EGFR mutations. METHODS Eligible patients between 2014 and 2019 were retrospectively identified and grouped into exon20 insertion mutations and major atypical mutations, which included G719X, L861Q and S768I. Disease-free survival (DFS) was evaluated in the entire cohort and stratified by radiologic characteristics. Recurrence patterns were investigated and compared between groups. A competing risk model was used to estimate the cumulative incidence of recurrence. RESULTS A total of 710 patients were finally included. Among them, 289 (40.7%) patients had exon 20 insertion mutations and 421 (59.3%) patients had major atypical mutations. There was no significant difference regarding DFS (P = 0.142) between groups in the entire cohort. The interaction between mutation subtype and the presence of ground-glass opacities was significant (hazard ratio 2.00, 95% confidence interval 1.59–2.51, P < 0.001), indicating DFS between exon 20 insertion mutations and major atypical mutations may be different among subsolid and solid tumours. Survival analysis consistently revealed no significant difference in subsolid tumours (P = 0.680), but favourable DFS of exon 20 insertion mutations in solid tumours (P = 0.037). Furthermore, patients with exon 20 insertion mutations had a lower risk of developing bone metastases did those with radiologic solid tumours (Gray’s test, P = 0.012). CONCLUSIONS Exon 20 insertion mutations were correlated with favourable DFS and lower incidence of bone metastases in radiologic solid lung adenocarcinomas harbouring atypical EGFR mutations.

Funder

National Key Research and Development Program of China

Ningbo Top Medical and Health Research Program

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine,Pulmonary and Respiratory Medicine,General Medicine,Surgery

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