Different prognosis of multiple lung cancer identified by 116-gene panel by next-generation sequencing based on an Asian population.

Abstract

Background: Patients with multiple lung cancer are becoming more common. The optimal criterion to distinguish multiple primary lung cancer (MPLC) from intrapulmonary metastases (IPM) is still unclear. In this study, we try to distinguish between MPLC and IPM and investigate their prognosis and risk factors.

Methods: This study was a retrospective analysis of patients with at least two malignant resected nodules in three medical centers from January 2019 to December 2019. Fifty-three patients with 130 lesions were enrolled and tested with 10-gene and 116-gene panels using next-generation sequencing (NGS). Disease-free survival (DFS) was defined as the time from surgery to either the date of the first recurrence (local or distant) or the last follow-up. The follow-up period was up to October 31, 2024. Tumor mutations were identified for each gene using the 116-gene and 10-gene panels, and clonal relatedness was identified by mutational profiling. Univariate and multivariate Cox regression analyses were conducted to identify independent risk factors for DFS.

Results: Fifty-three cases with 130 lesions met the inclusion criteria. A total of 16 recurrences were identified during follow-up. The 3- and 5-year DFS was 77.4% and 69.8%, respectively. According to the 116-gene panel, 35 (66.1%) cases favored MPLC, and 18 cases (33.9%) favored IPM on the basis of shared mutations. There was no difference in the 3-year DFS (82.9% vs. 66.7%, log-rank P=0.22), while there was an obvious difference in the 5-year DFS (80% vs. 60%, log-rank P=0.02). Univariate analysis showed alkaline phosphatase and forced expiratory volume in the first second percentage (FEV1%) as risk factors for metastasis (P=0.03 and P=0.003). Multivariate analysis showed that FEV1% was an independent factor (P=0.001). Cox regression analysis showed that the positive covariates were as follows: early stage [hazard ratio (HR) =4.192; 95% confidence interval (CI): 1.378 to 12.749; P=0.01] and MPLC (HR =0.187; 95% CI: 0.057 to 0.613; P=0.006).

Conclusions: NGS-based 116-gene panel classification can improve the accuracy of diagnosing MPLC and IPM. The diagnosis of IPM was associated with poor prognosis in Asian population.