Genetic alteration profile of EGFR-mutant resected IIB–IIIA stage NSCLC and correlation to clinical outcomes

Qiuhua Deng, Yuan Qiu, Junmei Jia, Hailing Tang, Liping Liu, Liyan Huang, Dongyun He, Xiaomeng Dong, Haihong Yang


Background: Genetic alteration profile of epidermal growth factor receptor (EGFR) mutant resected non- small cell lung cancer (NSCLC) and its relationship with clinical outcomes remains to be illustrated and genetic biomarkers that can predict recurrence need to be figured out.
Methods: Clinicopathological and follow-up information were collected for 99 EGFR-mutant resected NSCLC. Tumor sections were collected for genetic alteration detection. Targeted next-generation sequencing (NGS) was performed to detect somatic mutations within each sample using a 285-gene panel on the Ion Torrent platform.
Results: Concurrent driver gene mutations were detected in 86 participants. Adjuvant therapy was a positive factor in disease-free survival (DFS) period, and patients receiving tyrosine kinase inhibitors (TKIs) gained the longest DFS. A total of 34 concurrent mutant driver genes were found. The median number of mutated driver genes for each sample was 2 (range, 0–12). TP53 and NOTCH1 were the most frequent concurrent mutant driver genes with rates of 53.54% and 25.25% respectively. The number of concurrent mutant genes did not have a significant effect on recurrence. Multivariable analysis found that mutations of ATM (P=0.021), KIT (P=0.002), FGFR2 (P<0.001), MET (P=0.015), PDGFRA (P=0.042), RB1 (P=0.006), and wildtype NOTCH1 (P=0.032), ERBB4 (P=0.012), FGFR3 (P=0.035) were independent risk factors for the recurrence of resected EGFR mutant NSCLC.
Conclusions: TP53 and NOTCH1 was the most common concurrent mutant driver gene. Mutations of ATM, KIT, FGFR2, MET, PDGFRA, RB1, and wildtype NOTCH1, ERBB4, FGFR3 were independent risk factors for the recurrence of resected EGFR mutant NSCLC.